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Ivermectin

Distribution by Scientific Domains
Medical Sciences50%
Life Sciences28%
Chemistry19%
Distribution within Medical Sciences
General & Introductory Veterinary Medicine52%
Dermatology22%

Selected Abstracts

Single- and two-species tests to study effects of the anthelmintics ivermectin and morantel and the coccidiostatic monensin on soil invertebrates

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2009
John Jensen
Abstract Soil invertebrates in arable land are potentially exposed to veterinary medicines excreted by husbandry. The toxicity of three widely used pharmaceuticals was therefore investigated with the use of common soil invertebrates exposed in the laboratory in single- or two-species test system. The anthelmintic morantel did not cause significant mortality to either Folsomia fimetaria or Enchytraeus crypticus even at the highest tested concentration of 900 mg kg,1 dry soil. The coccidiostatic monensin affected the reproduction of F. fimetaria and E. crypticus with soil concentrations estimated to cause a 10% effect at values of approximately 109 and 71.8 mg kg,1 dry soil, respectively, but caused no mortality to adult. The anthelmintic ivermectin did not affect the survival of adult Hypoaspis aculeifer. Reproduction of H. aculeifer declined approximately 45% in response to ivermectin exposure of 5 mg kg,1 dry soil. Ivermectin was highly toxic to F. fimetaria and affected the survival of adults with soil concentrations estimated to cause a 50% mortality at values of 5.3 mg kg,1 dry soil in the single-species test system and 0.14 mg kg,1 dry soil in the two-species test system. Reproduction of F. fimetaria was reduced by ivermectin with 10% effective concentration at 0.19 mg kg,1 dry soil in the single-species test system and 0.02 mg kg,1 dry soil in two-species test system. It was shown that species interactions may influence the response of test organisms to toxic substances. The data from this study and previously published data showed that, whereas ivermectin is likely to pose a risk to soil-dwelling invertebrates, adverse effects of morantel and monensin are unlikely to occur as a result of residue excretion from treated farm animals. [source]

Behavioral effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2001
Jing Ding
Abstract Ivermectin is a potent antiparasitic drug against nematode and arthropod parasites. In this study, we examined the lethal and sublethal effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus. The median lethal concentration (LC50) at 72 h after ivermectin exposure was 560 nM. Sublethal endpoints focused on several stimulus-evoked locomotor behaviors: escape reflexes controlled by giant interneuron pathways, swimming and reversal, and crawling. Swimming, reversal, and crawling are controlled by nongiant interneuron pathways. Ivermectin inhibited swimming, reversal, crawling frequency, and crawling speed in a time- and concentration-dependent manner with a mean inhibitory concentration (IC50) at 3 h of 1.1, 16, 91, and 51nM, respectively. Ivermectin at 0.3 nM also significantly decreased the frequency of helical swimming waves. Picrotoxin, a Cl, channel blocker, antagonized the ivermectin-induced decrease in swimming frequency, crawling frequency, and crawling speed. There were no adverse effects on escape reflex 3 h after exposure to 300 nM ivermectin. Electrophysiological recordings showed that ivermectin had no effects on the conduction velocity of giant fiber systems. The results indicated that locomotor behaviors controlled by nongiant locomotor pathways were more sensitive to ivermectin than pathways controlled by giant interneurons and that Cl, channels may be involved in mediating ivermectin's inhibitory effects. [source]

Efficacy of chemical and botanical over-the-counter pediculicides available in Brazil, and off-label treatments, against head lice ex vivo

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2010
André Asenov MD
Background, There is a lack of reliable data on the efficacy of over-the-counter (OTC) pediculicides in Brazil. Methods, We performed ex vivo assays of eight marketed pediculicides: 1% permethrin (Kwell®, Clean Hair®, Keltrina®, Nedax®), 0.02% deltamethrin (Deltacid®, Pediderm®), and two "natural" products (Piolho e Lêndea®, Pilogenio®). We also tested 5% permethrin (Keltrina Plus®), traditional home remedies and an ivermectin-based product used in veterinary medicine. Head lice (49,52 per group) were immersed in the compound for 3 min and washed after 20 min to simulate the typical in vivo treatment protocol. Lice were examined for activity up to 24 h using stringent criteria for survival. Results, Of the permethrin containing products, highest mortality was observed with Kwell® and Clean Hair® (97.9 and 90.2% after 4 h). Keltrina®, Nedax®, Keltrina Plus®, and the two deltamethrin-based products showed only a low efficacy of <60% after 4 h. With exception of pure coconut oil (80% mortality after 4 h), home remedies showed a very low efficacy, and both marketed products killed few lice. The ivermectin-based product caused a mortality of 100% after 4 h. Conclusions, Most Brazilian OTC products did not show a satisfactory efficacy against head lice. Resistance may be present. Ivermectin and coconut oil are promising compounds for topical treatment. Laboratory-based tests should be used to assess resistance patterns and to identify formulations of the active ingredient that increase the efficacy. Standardized testing should be performed before a product is licensed for head lice treatment. [source]

Ivermectin: pharmacology and application in dermatology

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2005
Assen L. Dourmishev
Ivermectin is a synthetic derivative of the antiparasitic class of compounds known as avermectins. It is a macrolide endectocide with activity against both endoparasites with cutaneous tropism (Strongyloides stercoralis, Ancylostoma braziliense, Cochliomyia hominivorax, Dermatobia hominis, Filaria bancrofti, Wucheria malayi, Onchocerca volvulus, Loa-loa) and ectoparasites such as Sarcoptes scabies, Pediculus humanus, Demodex folliculorum, and Cheyletiella sp. Ivermectin is of great interest in the treatment of patients with different forms of scabies, head lice, demodecidosis, cutaneous larva migrans, cutaneous larva currens, myiasis, and filariasis. [source]

Efficacy of manual removal and ivermectin gavage for control of Salmincola californiensis (Wilson) infestation of chinook salmon, Oncorhynchus tshawytscha (Walbaum), captive broodstocks

JOURNAL OF FISH DISEASES, Issue 4 2001
K A Johnson
Captive broodstocks of spring chinook salmon, Oncorhynchus tshawytscha, were initiated from collections of naturally produced parr from the Lemhi River, a tributary of the Salmon River, ID, USA. These fish were subsequently demonstrated to be infested with the copepod parasite Salmincola californiensis. The initial prevalence of visible adult parasites for 4 years of observations made shortly after collection varied from 19.7 to 71.6%. Both the prevalence and intensity of the infestation increased in the freshwater culture of these fish. Manual removal was initiated as a means of control and practiced at monthly intervals. The number of Salmincola removed decreased in the ensuing 5 months, but the prevalence was not greatly affected. Ivermectin (22,23 dihydroavermectin), was diluted with saline and delivered by gavage at the rate of 0.20 mg kg,1 body weight when the groups were being handled for the manual removal of parasites. Either two or three ivermectin treatments were given to four broodstocks of chinook salmon depending on the severity of the infestation and on the extent of gill pathology. The combination of manual removal and ivermectin gavage eliminated live Salmincola and resolved all associated necrosis of the gill tissues. There was no trend to indicate that individual chinook salmon possessed a natural resistance to reinfestation. [source]

ESI+ MS/MS confirmation of canine ivermectin toxicity,

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2009
A. F. Lehner
Abstract Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations. In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30,50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization,Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na+ and K+ ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed. There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI+ MS/MS in samples originating from veterinary dosage forms. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Ivermectin Toxicity in 17 Collies

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2002
Kate Hopper
Ivermectin is widely used in veterinary medicine as an anthelminthic and generally has a wide margin of safety, but Collies are prone to ivermectin toxicity. Two groups of Collies were presented to the University of California Veterinary Medical Teaching Hospital (VMTH) with ivermectin toxicity. The medical records of the 2 groups of Collies were reviewed retrospectively. Group I comprised 5 adult Collies that received at least 400 ,g/kg ivermectin PO and were presented to the VMTH 3 hours after intoxication. These Collies showed marked clinical signs on presentation. Three of these dogs required mechanical ventilation and were euthanized for financial reasons; the remaining 2 dogs were comatose but recovered in 5,7 days. Group II was comprised of 12 adult Collies presented to the VMTH 2 days (n = 10) and 5 days (n = 2) after subcutaneous injection of 200,250 ,g/kg ivermectin. These animals showed greater variation in severity of illness among individuals; 5 animals progressed to stupor or coma, whereas 4 animals remained ambulatory. Most of these dogs' clinical signs deteriorated from the day of intoxication until approximately day 6, from which time they showed gradual but steady improvement. All of the Collies in this group survived, but it took 3 weeks for most of them to recover. Collies suffering from ivermectin toxicity can have a severe and prolonged clinical course requiring intensive nursing care. Respiratory, cardiovascular, and nutritional support may all be required. With appropriate care, however, the prognosis for complete recovery is good. [source]

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008
R. PÉREZ
In pregnant sheep at 120,130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 ± 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t½,). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 ± 0.6 ng/mL) and AUC (89.1 ± 11.4 ng·h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 ± 177.9 mL/kg) and lower values of t½, (8.0 ± 1.4 h) and mean residence time (8.0 ± 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment. [source]

Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007
L. OLSÉN
The pharmacokinetics of the histamine H1 -antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9,3.7 h) and the maximal plasma concentration 132 ng/mL (101,196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5,0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration,time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses. [source]

Endectocide residues affect insect attraction to dung from treated cattle: implications for toxicity tests

MEDICAL AND VETERINARY ENTOMOLOGY, Issue 4 2007
K. D. FLOATE
Abstract A 3-year study was performed in southern Alberta, Canada to assess the effect of endectocide residues on the attractiveness of cattle dung to colonizing insects. In 2003 and 2004, insect captures were compared between pitfall traps baited with dung of untreated cattle and paired traps baited with dung of cattle that had been treated 7 days previously with topically applied doramectin, eprinomectin, ivermectin or moxidectin. Faecal residues associated with each compound affected insect captures in both spring and autumn of each year. Effects were detected (P < 0.05) for a total of 94 cases representing 27 insect taxa from 13 families in three orders (Coleoptera, Diptera, Hymenoptera). Two-fold differences in captures were common. Up to six-fold differences were observed. Eleven cases of attraction and 11 cases of repellency were associated with residues of doramectin. Eprinomectin tended to repel insects, with decreased captures for 19 of 29 cases of effect. Ivermectin showed a strong attractive effect, with increased captures for 17 of 25 cases. Moxidectin also showed a strong attractive effect, with increased captures for 17 of 18 cases. Comparisons between compounds suggested that results for doramectin best predicted results for eprinomectin and vice versa. In 2005, insect captures were compared between pitfall traps baited with dung of untreated cattle and traps baited with dung from cattle treated 3, 7 or 14 days previously with topically applied doramectin. Effects were detected in 14 cases plus one case of near significance (P= 0.053). Significant differences between control vs. days 3, 7 and/or 14 dung were detected in nine cases. Residues enhanced captures in seven of these cases. Day 14 dung affected captures in six of these cases. This study shows that endectocide residues can affect the number of insects attracted to colonize and oviposit in dung. Hence, the emergence of their offspring from field-colonized dung of untreated vs. endectocide-treated cattle should not be used as a measure of residue toxicity per se, but rather as a measure of ,insect activity'. Insect activity is a composite measure of residue toxicity, the number and species composition of insect colonists, and the mortality factors (e.g. predation, parasitism, competition) associated with the co-occurrence of these species in the dung pat. [source]

Semi-automated quantification of ivermectin in rat and human plasma using protein precipitation and filtration with liquid chromatography/tandem mass spectrometry

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2004
Tony Pereira
Ivermectin is a parasiticide commonly used in humans and livestock. It is currently under development for the treatment of pediculosis of humans (head lice) that does not respond to established treatments. A liquid chromatography/turbo ion spray tandem mass spectrometry (LC/TIS-MS/MS) method for the determination of ivermectin in rat and human plasma has been developed that uses emamectin [4,-epi-(methylamino)-4,-deoxyavermectin] as the internal standard. Sample preparation involved protein precipitation and filtration of fortified plasma in the 96-well format. Chromatographic separation was accomplished using fast gradient conditions on a C8 stationary phase. The analytes were detected with the mass spectrometer operated in the positive ion, multiple reaction monitoring mode. The method exhibited good intra- and interday accuracy and precision, and was linear over a dynamic range of 1,2000,ng/mL. In rat plasma, intraday accuracy ranged between 84,93% for the low quality control (QC) sample (1.5 ng/mL), and between 91,109% for the remaining QCs. Intraday precision ranged between 4.9,15% for the low QC, and 0.8,6.3% for the remaining QCs. Interday accuracy ranged between 88,107%, and precision between 4.1,11%. Similar data was obtained using human plasma. An investigation of matrix effects indicated that the ionization efficiency of ivermectin was favored by the presence of an ammonium ion in an aqueous environment. The implications of this observation toward assay sensitivity are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Treatment of head lice

DERMATOLOGIC THERAPY, Issue 4 2009
Stephanie A. Diamantis
ABSTRACT Pediculosis capitis, or head lice, is a common infestation among children worldwide. Multiple therapies exist for the treatment of this condition, including topical pediculicides and oral medications. When used in combination with environmental decontamination, these drugs can be very effective in eradicating head lice infestation without significant adverse events. The present study discusses the use of available over-the-counter and prescription treatments, including pyrethroids and permethrin, lindane, malathion, ivermectin, and trimethoprim-sulfamethoxazole, in the treatment of head lice. [source]

Single- and two-species tests to study effects of the anthelmintics ivermectin and morantel and the coccidiostatic monensin on soil invertebrates

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2009
John Jensen
Abstract Soil invertebrates in arable land are potentially exposed to veterinary medicines excreted by husbandry. The toxicity of three widely used pharmaceuticals was therefore investigated with the use of common soil invertebrates exposed in the laboratory in single- or two-species test system. The anthelmintic morantel did not cause significant mortality to either Folsomia fimetaria or Enchytraeus crypticus even at the highest tested concentration of 900 mg kg,1 dry soil. The coccidiostatic monensin affected the reproduction of F. fimetaria and E. crypticus with soil concentrations estimated to cause a 10% effect at values of approximately 109 and 71.8 mg kg,1 dry soil, respectively, but caused no mortality to adult. The anthelmintic ivermectin did not affect the survival of adult Hypoaspis aculeifer. Reproduction of H. aculeifer declined approximately 45% in response to ivermectin exposure of 5 mg kg,1 dry soil. Ivermectin was highly toxic to F. fimetaria and affected the survival of adults with soil concentrations estimated to cause a 50% mortality at values of 5.3 mg kg,1 dry soil in the single-species test system and 0.14 mg kg,1 dry soil in the two-species test system. Reproduction of F. fimetaria was reduced by ivermectin with 10% effective concentration at 0.19 mg kg,1 dry soil in the single-species test system and 0.02 mg kg,1 dry soil in two-species test system. It was shown that species interactions may influence the response of test organisms to toxic substances. The data from this study and previously published data showed that, whereas ivermectin is likely to pose a risk to soil-dwelling invertebrates, adverse effects of morantel and monensin are unlikely to occur as a result of residue excretion from treated farm animals. [source]

Behavioral effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2001
Jing Ding
Abstract Ivermectin is a potent antiparasitic drug against nematode and arthropod parasites. In this study, we examined the lethal and sublethal effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus. The median lethal concentration (LC50) at 72 h after ivermectin exposure was 560 nM. Sublethal endpoints focused on several stimulus-evoked locomotor behaviors: escape reflexes controlled by giant interneuron pathways, swimming and reversal, and crawling. Swimming, reversal, and crawling are controlled by nongiant interneuron pathways. Ivermectin inhibited swimming, reversal, crawling frequency, and crawling speed in a time- and concentration-dependent manner with a mean inhibitory concentration (IC50) at 3 h of 1.1, 16, 91, and 51nM, respectively. Ivermectin at 0.3 nM also significantly decreased the frequency of helical swimming waves. Picrotoxin, a Cl, channel blocker, antagonized the ivermectin-induced decrease in swimming frequency, crawling frequency, and crawling speed. There were no adverse effects on escape reflex 3 h after exposure to 300 nM ivermectin. Electrophysiological recordings showed that ivermectin had no effects on the conduction velocity of giant fiber systems. The results indicated that locomotor behaviors controlled by nongiant locomotor pathways were more sensitive to ivermectin than pathways controlled by giant interneurons and that Cl, channels may be involved in mediating ivermectin's inhibitory effects. [source]

A review of the use of moxidectin in horses

EQUINE VETERINARY EDUCATION, Issue 10 2008
J. Schumacher
Summary Moxidectin has broad-spectrum anti-nematodal and anti-arthropodal activities in the horse but is not effective against tapeworms or flukes. Moxidectin and ivermectin have the same efficacy against internal, adult parasites of horses. Moxidectin, however, is highly effective in eliminating encysted and hypobiotic larval stages of cyathostomins, whereas ivermectin is not. Treatment of horses with moxidectin results in an egg-reappearance period (ERP) of 15,24 weeks. Because of its long ERP, moxidectin is labelled to be used at 12 week intervals. Moxidectin may provide protection against infection by ingested cyathostomin larvae for 2,3 weeks after it is administered. The larvicidal activity of moxidectin has often been compared to that of fenbendazole administered at either 7.5 or 10 mg/kg bwt for 5 consecutive days. The efficacy of fenbendazole, when administered daily for 5 consecutive days at 7.5 or 10 mg/kg bwt, against all stages of cyathostomins is often less than that of moxidectin because resistance of cyathostomins to benzimidazoles is prevalent worldwide, and the 5 day course of fenbendazole does not overcome this resistance. There are now reports of resistance of ascarids to moxidectin. Overt resistance of cyathostomins and a shortened egg re-emergence period after treatment with moxidectin have been reported. Rapid removal of manure by natural fauna can significantly reduce larval nematode concentrations and thereby reduce intervals of anthelmintic treatment. Of the macrocyclic lactones, moxidectin has the least deleterious effect on faecal fauna. [source]

Microarray analysis of acaricide-inducible gene expression in the southern cattle tick, Rhipicephalus (Boophilus) microplus

INSECT MOLECULAR BIOLOGY, Issue 6 2008
L. Saldivar
Abstract Acaricide-inducible differential gene expression was studied in larvae of Rhipicephalus (Boophilus) microplus using a microarray-based approach. The acaricides used were: coumaphos, permethrin, ivermectin, and amitraz. The microarrays contained over 13 000 probes, having been derived from a previously described R. microplus gene index (BmiGI Version 2; Wang et al., 2007). Relative quantitative reverse transcriptase-PCR, real time PCR, and serial analysis of gene expression data was used to verify microarray data. Among the differentially expressed genes with informative annotation were legumain, glutathione S-transferase, and a putative salivary gland-associated protein. [source]

Efficacy of chemical and botanical over-the-counter pediculicides available in Brazil, and off-label treatments, against head lice ex vivo

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2010
André Asenov MD
Background, There is a lack of reliable data on the efficacy of over-the-counter (OTC) pediculicides in Brazil. Methods, We performed ex vivo assays of eight marketed pediculicides: 1% permethrin (Kwell®, Clean Hair®, Keltrina®, Nedax®), 0.02% deltamethrin (Deltacid®, Pediderm®), and two "natural" products (Piolho e Lêndea®, Pilogenio®). We also tested 5% permethrin (Keltrina Plus®), traditional home remedies and an ivermectin-based product used in veterinary medicine. Head lice (49,52 per group) were immersed in the compound for 3 min and washed after 20 min to simulate the typical in vivo treatment protocol. Lice were examined for activity up to 24 h using stringent criteria for survival. Results, Of the permethrin containing products, highest mortality was observed with Kwell® and Clean Hair® (97.9 and 90.2% after 4 h). Keltrina®, Nedax®, Keltrina Plus®, and the two deltamethrin-based products showed only a low efficacy of <60% after 4 h. With exception of pure coconut oil (80% mortality after 4 h), home remedies showed a very low efficacy, and both marketed products killed few lice. The ivermectin-based product caused a mortality of 100% after 4 h. Conclusions, Most Brazilian OTC products did not show a satisfactory efficacy against head lice. Resistance may be present. Ivermectin and coconut oil are promising compounds for topical treatment. Laboratory-based tests should be used to assess resistance patterns and to identify formulations of the active ingredient that increase the efficacy. Standardized testing should be performed before a product is licensed for head lice treatment. [source]

ESI+ MS/MS confirmation of canine ivermectin toxicity,

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2009
A. F. Lehner
Abstract Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations. In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30,50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization,Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na+ and K+ ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed. There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI+ MS/MS in samples originating from veterinary dosage forms. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Simultaneous determination of avermectins in bovine tissues by LC-MS/MS

JOURNAL OF SEPARATION SCIENCE, JSS, Issue 21 2009
Koichi Inoue
Abstract Analytical method for the simultaneous quantification of avermectins (AVMs), abamectin B1a, abamectin 8,9-Z isomer B1a, emamectine benzoate B1a, emamectine benzoate 8,9-Z isomer B1a, ivermectin, eprinomectin B1a, doramectin and moxidectin in bovine tissues (muscle, liver and fat) was developed by LC-MS/MS in electrospray positive ion mode. The separation was achieved on a short TSK-GEL ODS 100V column with the mobile phase consisting of acetonitrile and aquatic 0.1,mM ammonium formate containing 0.1% formic acid v/v at a flow rate of 0.2,mL/min with gradient elution. Liquid,liquid extraction with isooctane was used for the sample extraction/preparation of analytes in bovine samples. The linearity of the calibration curves was excellent in matrix-matched standards, and yielded the coefficients (r2=0.997,0.999, range from LOQ to 500, 1000 or 5000,ng/g) of determination of the target analytes. Recoveries were in the range of 87.9,99.8% with associated precision values (within-day: 1.5,7.4%, n=6, and between-day: 1.5,8.4% for 3 days) for repeatability and reproducibility. LC-MS/MS method has been proven to be highly efficient and suitable for the simultaneous determinations of eight AVMs in bovine tissue samples. [source]

Ivermectin Toxicity in 17 Collies

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2002
Kate Hopper
Ivermectin is widely used in veterinary medicine as an anthelminthic and generally has a wide margin of safety, but Collies are prone to ivermectin toxicity. Two groups of Collies were presented to the University of California Veterinary Medical Teaching Hospital (VMTH) with ivermectin toxicity. The medical records of the 2 groups of Collies were reviewed retrospectively. Group I comprised 5 adult Collies that received at least 400 ,g/kg ivermectin PO and were presented to the VMTH 3 hours after intoxication. These Collies showed marked clinical signs on presentation. Three of these dogs required mechanical ventilation and were euthanized for financial reasons; the remaining 2 dogs were comatose but recovered in 5,7 days. Group II was comprised of 12 adult Collies presented to the VMTH 2 days (n = 10) and 5 days (n = 2) after subcutaneous injection of 200,250 ,g/kg ivermectin. These animals showed greater variation in severity of illness among individuals; 5 animals progressed to stupor or coma, whereas 4 animals remained ambulatory. Most of these dogs' clinical signs deteriorated from the day of intoxication until approximately day 6, from which time they showed gradual but steady improvement. All of the Collies in this group survived, but it took 3 weeks for most of them to recover. Collies suffering from ivermectin toxicity can have a severe and prolonged clinical course requiring intensive nursing care. Respiratory, cardiovascular, and nutritional support may all be required. With appropriate care, however, the prognosis for complete recovery is good. [source]

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008
R. PÉREZ
In pregnant sheep at 120,130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 ± 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t½,). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 ± 0.6 ng/mL) and AUC (89.1 ± 11.4 ng·h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 ± 177.9 mL/kg) and lower values of t½, (8.0 ± 1.4 h) and mean residence time (8.0 ± 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment. [source]

Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007
L. OLSÉN
The pharmacokinetics of the histamine H1 -antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9,3.7 h) and the maximal plasma concentration 132 ng/mL (101,196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5,0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration,time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses. [source]

Moxidectin and ivermectin metabolic stability in sheep ruminal and abomasal contents

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2005
A. LIFSCHITZ
The oral administration of macrocyclic lactones to sheep leads to poorer efficacy and shorter persistence of the antiparasitic activity compared to the subcutaneous treatment. Gastrointestinal biotransformation occurring after oral treatment to ruminant species has been considered as a possible cause of the differences observed between routes of administration. The current work was addressed to evaluate on a comparative basis the in vitro metabolism of moxidectin (MXD) and ivermectin (IVM) in sheep ruminal and abomasal contents. Both compounds were incubated under anaerobic conditions during 2, 6 and 24 h in ruminal and abomasal contents collected from untreated adult sheep. Drug concentrations were measured by high-performance liquid chromatography with fluorescence detection after sample clean up and solid phase extraction. Neither MXD nor IVM suffered metabolic conversion and/or chemical degradation after 24-h incubation in ruminal and abomasal contents collected from adult sheep. Unchanged MXD and IVM parent compounds represented between 95.5 and 100% of the total drug recovered in the ruminal and abomasal incubation mixtures compared with those measured in inactive control incubations. The partition of both molecules between the solid and fluid phases of both sheep digestive contents was assessed. MXD and IVM were extensively bound (>90%) to the solid material of both ruminal and abomasal contents collected from sheep fed on lucerne hay. The results reported here confirm the extensive degree of association to the solid digestive material and demonstrates a high chemical stability without evident metabolism and/or degradation for both MXD and IVM in ruminal and abomasal contents. [source]

Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian Shepherd

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005
J. GEYER
A subpopulation of dogs of the Collie and Australian Shepherd breeds show increased sensitivity to central nervous actions of ivermectin, doramectin, loperamide, and probably several other drugs. The molecular background for this greater sensitivity is a nonsense mutation in the MDR1 efflux pump, which is part of the functional blood,brain barrier and normally limits drug penetration into the brain. This report describes a rapid PCR-based method for detection of this nt230(del4) MDR1 mutation using a small amount of genomic DNA from blood cells. Thereby, homozygous intact, homozygous mutated, and heterozygous mutated MDR1 genotypes can be clearly differentiated by high resolution polyacrylamide gel electrophoresis. Using this diagnostic test two Collies and one Australian Shepherd were screened for the nt230(del4) MDR1 mutation. The Collies had no history of altered drug sensitivity and showed homozygous intact and heterozygous mutated MDR1 alleles, respectively. However, the Australian Shepherd developed clear signs of neurotoxicity including ataxia, crawling, acoustic and tactile hyperexcitability, and miosis after a single dose of moxidectin (400 ,g/kg). For this dog two mutated MDR1 alleles were detected. This report describes for the first time moxidectin neurotoxicosis in a dog with a homozygous MDR1 mutation. [source]

Therapeutic implications of the MDR-1 gene

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004
K. L. Mealey
Drug transporters significantly influence drug pharmacokinetics and pharmacodynamics. P-glycoprotein (P-gp), the product of the MDR1 (ABCB1) gene, is among the most well-characterized drug transporters, particularly in veterinary medicine. A number of clinically relevant, structurally and functionally unrelated drugs are substrates for P-gp. P-gp is expressed by a variety of normal tissues including the intestines, renal tubular cells, brain capillary endothelial cells, biliary canalicular cells, and others, where it functions to actively extrude substrate drugs. In this capacity, P-gp limits oral absorption and central nervous system entry of many substrate drugs. A number of MDR1 polymorphisms have been described in human patients, some of which result in altered drug pharmacokinetics and susceptibility to diseases such as Parkinson's disease, inflammatory bowel disease, refractory seizures, and others. An MDR1 polymorphism in herding breed dogs, including collies and Australian shepherds, has been demonstrated to be the cause of ivermectin sensitivity in these breeds. Recent evidence suggests that this polymorphism, a 4-bp deletion mutation, results in increased susceptibility to the toxicity of several drugs in addition to ivermectin. Furthermore, data in rodent models suggest that P-gp may play an important role in regulating the hypothalamic,pituitary,adrenal axis. [source]

Treatment of northern fur seal (Callorhinus ursinus) pups with ivermectin reduces hookworm-induced mortality

MARINE MAMMAL SCIENCE, Issue 4 2009
Robert L. DeLong
[source]

Sheep blowfly strike risk and management in Great Britain: a survey of current practice

MEDICAL AND VETERINARY ENTOMOLOGY, Issue 4 2008
B. BISDORFF
Abstract The methods used for the control of sheep blowfly strike (ovine cutaneous myiasis) and the farm management factors associated with strike prevalence were examined using data from questionnaire survey returns provided by 966 sheep farmers in Great Britain, based on the period between March 2003 and February 2004. Overall, 91% of participants treated prophylactically with insecticides against blowfly strike; 39% treated twice and 11% treated more than three times in the year. Insect growth regulators (IGRs) were the most commonly chosen product (40%), especially the IGR cyromazine. Only 12% of farmers opted to dip their sheep in organophosphate insecticide against fly strike and 2% of farmers reported applying inappropriate products against strike to their sheep, such as ivermectin or ,drenches'. Farmers worming their ewes more often were 0.8 times less likely to report blowfly strike, but those who wormed their lambs more often were 1.2 times more likely to report strike. Pure-breed flocks were 0.7 times less likely to record an outbreak of blowfly strike than cross-breed flocks. Strike was less likely in ewe flocks grazed at higher altitude; however, this relationship with altitude was not seen in lambs. The results show that insecticides remain the primary tool used by almost all farmers to prevent strike and that the type of insecticides used and means of application have altered dramatically over the past 15 years. However, the prevalence of strike has remained almost unchanged over this period. Clearly careful attention to the type and timing of insecticide application, in association with a detailed understanding of the husbandry factors that predispose sheep to higher strike risk, is essential to allow the optimal management of strike problems. [source]

Endectocide residues affect insect attraction to dung from treated cattle: implications for toxicity tests

MEDICAL AND VETERINARY ENTOMOLOGY, Issue 4 2007
K. D. FLOATE
Abstract A 3-year study was performed in southern Alberta, Canada to assess the effect of endectocide residues on the attractiveness of cattle dung to colonizing insects. In 2003 and 2004, insect captures were compared between pitfall traps baited with dung of untreated cattle and paired traps baited with dung of cattle that had been treated 7 days previously with topically applied doramectin, eprinomectin, ivermectin or moxidectin. Faecal residues associated with each compound affected insect captures in both spring and autumn of each year. Effects were detected (P < 0.05) for a total of 94 cases representing 27 insect taxa from 13 families in three orders (Coleoptera, Diptera, Hymenoptera). Two-fold differences in captures were common. Up to six-fold differences were observed. Eleven cases of attraction and 11 cases of repellency were associated with residues of doramectin. Eprinomectin tended to repel insects, with decreased captures for 19 of 29 cases of effect. Ivermectin showed a strong attractive effect, with increased captures for 17 of 25 cases. Moxidectin also showed a strong attractive effect, with increased captures for 17 of 18 cases. Comparisons between compounds suggested that results for doramectin best predicted results for eprinomectin and vice versa. In 2005, insect captures were compared between pitfall traps baited with dung of untreated cattle and traps baited with dung from cattle treated 3, 7 or 14 days previously with topically applied doramectin. Effects were detected in 14 cases plus one case of near significance (P= 0.053). Significant differences between control vs. days 3, 7 and/or 14 dung were detected in nine cases. Residues enhanced captures in seven of these cases. Day 14 dung affected captures in six of these cases. This study shows that endectocide residues can affect the number of insects attracted to colonize and oviposit in dung. Hence, the emergence of their offspring from field-colonized dung of untreated vs. endectocide-treated cattle should not be used as a measure of residue toxicity per se, but rather as a measure of ,insect activity'. Insect activity is a composite measure of residue toxicity, the number and species composition of insect colonists, and the mortality factors (e.g. predation, parasitism, competition) associated with the co-occurrence of these species in the dung pat. [source]

Semi-automated quantification of ivermectin in rat and human plasma using protein precipitation and filtration with liquid chromatography/tandem mass spectrometry

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2004
Tony Pereira
Ivermectin is a parasiticide commonly used in humans and livestock. It is currently under development for the treatment of pediculosis of humans (head lice) that does not respond to established treatments. A liquid chromatography/turbo ion spray tandem mass spectrometry (LC/TIS-MS/MS) method for the determination of ivermectin in rat and human plasma has been developed that uses emamectin [4,-epi-(methylamino)-4,-deoxyavermectin] as the internal standard. Sample preparation involved protein precipitation and filtration of fortified plasma in the 96-well format. Chromatographic separation was accomplished using fast gradient conditions on a C8 stationary phase. The analytes were detected with the mass spectrometer operated in the positive ion, multiple reaction monitoring mode. The method exhibited good intra- and interday accuracy and precision, and was linear over a dynamic range of 1,2000,ng/mL. In rat plasma, intraday accuracy ranged between 84,93% for the low quality control (QC) sample (1.5 ng/mL), and between 91,109% for the remaining QCs. Intraday precision ranged between 4.9,15% for the low QC, and 0.8,6.3% for the remaining QCs. Interday accuracy ranged between 88,107%, and precision between 4.1,11%. Similar data was obtained using human plasma. An investigation of matrix effects indicated that the ionization efficiency of ivermectin was favored by the presence of an ammonium ion in an aqueous environment. The implications of this observation toward assay sensitivity are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Strongyloides Stercoralis Hyperinfection Transmitted by Liver Allograft in a Transplant Recipient

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009
M. J. Rodriguez-Hernandez
We describe a case of Strongyloides stercoralis hyperinfection in a liver allograft recipient 2.5 months after transplantation. The patient lives in Spain, which is not considered an endemic country for strongyloidiasis, and denied prior residence or travel to any known endemic area. The initial symptoms were fever and vomiting, and he subsequently developed a severe respiratory disease. An endoscopic biopsy of ulcerative lesions of the duodenum revealed massive mucosa infiltration by larvae and adult worms, which were also found in respiratory samples. The patient was successfully treated with combined therapy with albendazole and ivermectin. The strongyloides infection was transmitted by the liver allograft. The donor was from Ecuador and, retrospectively, his serum tested positive for S. stercoralis IgG antibodies. Additionally, the pancreas,left kidney allograft recipient from the same donor later developed an intestinal strongyloidiasis without hyperinfection syndrome. To our knowledge, this is the first confirmed case of S. stercoralis infection transmission from the same donor to two solid allograft recipients. [source]