Home About us Contact
|
Home About us Contact | ||
|
|
||
Healthy Human Volunteers (healthy + human_volunteer)
Selected AbstractsEFFECTS OF AGAR AND PECTIN ON GASTRIC EMPTYING AND POST-PRANDIAL GLYCAEMIC PROFILES IN HEALTHY HUMAN VOLUNTEERSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Masaki Sanaka SUMMARY 1Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [13C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [13CO2] excretion time () and the time for maximal [13CO2] excretion rate (tlag) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t -test with Bonferroni adjustment. 3The time-course for respiratory [13CO2] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [13CO2] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t -test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t -test). Among the three meals, significant differences were found in (P = 0.002, anova) and tlag (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged (P = 0.007 and P < 0.0001, respectively, Student's t -test) and tlag (P = 0.006 and P = 0.002, respectively, Student's t -test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response. [source] Radioprotective effects of Daflon against genotoxicity induced by gamma irradiation in human cultured lymphocytesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009Seyed Jalal Hosseinimehr Abstract The ability of Daflon to protect against genotoxicity induced by gamma irradiation has been investigated in vivo and in vitro in cultured lymphocytes from healthy human volunteers. Peripheral human blood samples were collected predose (10 min before) and 1, 2, and 3 hr after a single oral ingestion of 1000 mg of Daflon. At each time point, whole blood was exposed in vitro to 150 cGy of cobalt-60 gamma rays, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. For each volunteer, the results showed a significant increase in the incidence of micronuclei after exposure to gamma irradiation as compared to control unexposed samples. As early as 1 hr after Daflon administration, a significant decrease in the incidence of micronuclei was observed in comparison with similarly irradiated lymphocytes collected before administration. The maximum protection was reached 1 hr after administration of Daflon with a significant decrease in the frequency of micronuclei of 40%. These findings suggest the possible application of Daflon for the protection of human lymphocytes from the genetic damage and side effects induced by gamma irradiation. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source] Which neuroreceptors mediate the subjective effects of MDMA in humans?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2001A summary of mechanistic studies Abstract In preclinical studies, 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') has been shown to release serotonin (5-HT), dopamine and norepinephrine. However, the role of these neurotransmitters and their corresponding receptor sites in mediating the subjective effects of MDMA has not yet been studied in humans. Therefore, we investigated the effects of three different neuroreceptor pretreatments on the subjective, cardiovascular and adverse effects of MDMA (1.5 mg/kg orally) in 44 healthy human volunteers. Pretreatments were: the selective serotonin reuptake inhibitor citalopram (40 mg intravenously) in 16 subjects, the 5-HT2 antagonist ketanserin (50 mg orally) in 14 subjects, and the D2 antagonist haloperidol (1.4 mg intravenously) in 14 subjects. Each of these studies used a double-blind placebo-controlled within-subject design and all subjects were examined under placebo, pretreatment, MDMA and pretreatment plus MDMA conditions. Citalopram markedly reduced most of the subjective effects of MDMA, including positive mood, increased extraversion and self-confidence. Cardiovascular and adverse effects of MDMA were also attenuated by citalopram. Haloperidol selectively reduced MDMA-induced positive mood but had no effect on other subjective effects of MDMA or the cardiovascular or adverse responses to MDMA. Ketanserin selectively reduced MDMA-induced perceptual changes and emotional excitation. These results indicate that the overall psychological effects of MDMA largely depend on carrier-mediated 5-HT release, while the more stimulant-like euphoric mood effects of MDMA appear to relate, at least in part, to dopamine D2 receptor stimulation. The mild hallucinogen-like perceptual effects of MDMA appear to be due to serotonergic 5-HT2 receptor stimulation. Copyright © 2001 John Wiley & Sons, Ltd. [source] Ethics of studies involving human volunteers.INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2007The importance to the personal products industry of testing novel products in healthy human volunteers and the need to ensure the trials were both safe and ethical were addressed in part I. The historical development of ethical standards for human testing was also summarized. The present paper highlights the ethical principles to be considered when testing novel non-medicinal products on human volunteers, and it describes how they can be implemented in a pragmatic manner to avoid delay to the sponsor's research program. The structure and function of ethics committees is discussed. [source] Pralidoxime and l -lactate effects in vitro on the inhibition of acetylcholinesterase by paraoxon: pralidoxime does not confer superior protectionJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2001Georg Petroianu Abstract Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Although oximes are the only enzyme reactivators presently available, clinical experience with their use was rather disappointing. Recent work has shown that under certain conditions l -lactate is also able to reduce in vitro the POX inhibition of butyrylcholine- and acetylcholineesterase (BChE and AChE). To assess the practical relevance, if any, of these findings, the protective effects of pralidoxime (PRX) and those of lactate had to be compared in the same in vitro model. Effects of PRX on the inhibition of AChE by POX were assessed in vitro in plasma of 12 (six male and six female) healthy human volunteers. The determinations were repeated using different oxime and different POX concentrations. The AChE activity determinations were performed using the following sampler: sample BL,baseline (or untreated plasma); sample a,after addition of POX to plasma (pl + POX); sample b,after POX and plasma were incubated and then oxime was added (pl + POX/PRX); sample c,after addition of oxime to plasma (pl + PRX); sample d,after oxime and plasma were incubated and then POX was added (pl + PRX/POX); sample e,after oxime and POX were incubated and then added to plasma (PRX + POX/pl). Results were corrected for spurious enzyme ,pseudo-activity' due to interaction between PRX and substrate (acetylthiocholine) in the absence of enzyme. In the micro- and millimolar ranges, PRX is able to protect in vitro AChE from inhibition by POX when added to human plasma prior to POX or when incubated with POX prior to addition to plasma. Adding PRX to plasma after POX has no protective effect. The PRX results were compared statistically with historical lactate data (obtained under identical conditions) using the Wilcoxon matched pairs test, with significance assumed for p = 0.01. No difference between PRX and lactate's protective effect on the AChE inhibition by POX was found in the in vitro model used. We therefore conclude that in vivo testing of lactate as a POX protective agent is warranted. Copyright © 2001 John Wiley & Sons, Ltd. [source] Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteersJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005W. Ridtitid MD FCFPT Summary Background:, Antimalarial mefloquine has a structure related to quinine. The major metabolite of quinine is 3-hydroxyquinine formed by cytochrome P450 3A4 (CYP3A4). Ketoconazole, a potent inhibitor of CYP3A4, is known to markedly increase plasma concentrations of various co-administered drugs including quinine. Objective:, To assess the effect of ketoconazole on plasma concentrations of mefloquine in healthy Thai male volunteers. Methods:, In an open, randomized two-phase crossover study separated by a 1-month period, eight healthy Thai male volunteers received a single oral dose of 500 mg mefloquine alone or co-administration with 400 mg/day ketoconazole orally for 10 days. Serial blood samples were collected at specific time points for a 56-day period. Plasma mefloquine and mefloquine carboxylic metabolite concentrations during 56 days were measured by a modified and validated high-performance liquid chromatographic method with UV detection. Results:, Co-administration with ketoconazole markedly increased the mean values of mefloquine AUC0,t, t1/2, and Cmax when compared with mefloquine alone by 79% (P < 0·001), 39% (P < 0·05) and 64% (P < 0·001) respectively. The AUC0,t,, and Cmax of mefloquine carboxylic acid metabolite were decreased by 28% (P < 0·05) and 31% (P < 0·05), respectively when compared with mefloquine alone. Conclusions:, Co-administration with ketoconazole increased plasma mefloquine concentrations in healthy human volunteers. One of possible mechanisms of the increase in plasma mefloquine concentrations may be the result of the inhibition of CYP3A4 by ketoconazole. In case of mefloquine is co-administered with ketoconazole, drug,drug interactions should be recognized and the dose of mefloquine should be adjusted to maximize the therapeutic efficacy and to reduce the cost of therapy. [source] In-vitro Antioxidant and In-vivo Photoprotective Effect of Three Lyophilized Extracts of Sedum telephium L. LeavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000FRANCESCO BONINA Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13 000 and 13 500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage. [source] The role of the fibrocyte in intimal hyperplasiaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006R. L. VARCOE Summary.,Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (, -SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and , -SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and , -SMA) and also to double stain for CD34 and , -SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury. [source] Effects of subanaesthetic and anaesthetic doses of sevoflurane on regional cerebral blood flow in healthy volunteers.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2004A positron emission tomographic study Background:, We tested the hypothesis that escalating drug concentrations of sevoflurane are associated with a significant decline of cerebral blood flow in regions subserving conscious brain activity, including specifically the thalamus. Methods:, Nine healthy human volunteers received three escalating doses using 0.4%, 0.7% and 2.0% end-tidal sevoflurane inhalation. During baseline and each of the three levels of anaesthesia one PET scan was performed after injection of . Cardiovascular and respiratory parameters were monitored and electroencephalography and bispectral index (BIS) were registered. Results:, Sevoflurane decreased the BIS values dose-dependently. No significant change in global cerebral blood flow (CBF) was observed. Increased regional CBF (rCBF) in the anterior cingulate (17,21%) and decreased rCBF in the cerebellum (18,35%) were identified at all three levels of sedation compared to baseline. Comparison between adjacent levels sevoflurane initially (0 vs. 0.2 MAC) decreased rCBF significantly in the inferior temporal cortex and the lingual gyrus. At the next level (0.2 MAC vs. 0.4 MAC) rCBF was increased in the middle temporal cortex and in the lingual gyrus, and decreased in the thalamus. At the last level (0.4 MAC vs. 1 MAC) the rCBF was increased in the insula and decreased in the posterior cingulate, the lingual gyrus, precuneus and in the frontal cortex. Conclusion:, At sevoflurane concentrations at 0.7% and 2.0% a significant decrease in relative rCBF was detected in the thalamus. Interestingly, some of the most profound changes in rCBF were observed in structures related to pain processing (anterior cingulate and insula). [source] Selective bio-availability of phenolic acids from Scottish strawberriesMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue S1 2009Wendy R. Russell Abstract Scottish strawberries were found to be a rich source of phenolic acids, namely benzoic (1287.95 ± 279.98 mg/kg) and cinnamic (1159.40 ± 233.96 mg/kg) acids, both free and attached to other plant components. Studies suggest a chemopreventative role for such compounds in several major clinical conditions, but the anticipated benefits are likely to be affected by their bio-availability and metabolic fate. In this pilot study, strawberries (750 g) was consumed by four healthy human volunteers (32 ± 6 years). Only the benzoic acids were detected in the plasma. Of these, the major free (gentisic, protocatechuic and p -hydroxybenzoic acid) and conjugated (syringic acid) benzoic acids were 26,27% recovered in the urine within 5 h. Cinnamic acids were completely undetected in plasma and only trace amounts were found in the urine. Since, the cinnamic acids escaped absorption early in the gastrointestinal tract, their release and/or metabolism is dependant on the host colonic microbiota. Results indicate that there is a high degree of selective absorption of strawberry phenolic acids into the systemic circulation. If selective absorption of phenolic acids is observed with consumption of other plant-based foods, this is likely to have implications for the bioactive role of these compounds in chronic disease prevention. [source] Proton T2 relaxation of cerebral metabolites of normal human brain over large TE rangeNMR IN BIOMEDICINE, Issue 1 2005E. E. Brief Abstract T2 of NAA, creatine and choline-containing compounds were measured in posterior frontal white matter and occipital grey matter in 10 healthy human volunteers. Decay curves comprised signals from eight TE times ranging from 30 to 800,ms with TR 2000,ms acquired with a PRESS sequence on a 1.5,T clinical scanner. Simulations were conducted to assess the precision of T2 estimates from decay curves comprising varying numbers and ranges of TE points. Mean and standard errors for T2s of NAA, creatine and choline-containing compounds were 300(8), 169(3) and 239(4) ms in posterior frontal white matter and 256(6), 159(8) and 249(8) ms in occipital grey matter. In vivoT2s found for choline and NAA were shorter than the T2s in the literature. The elevation of literature T2s is accounted for by the simulation results, which demonstrated that there is a bias towards lengthened T2s when T2 is measured with a maximum TE , T2. Concentration estimates are at risk of being underestimated if previously reported T2 corrections are used. Copyright © 2004 John Wiley & Sons, Ltd. [source] Repair of cyclobutyl pyrimidine dimers in human skin: variability among normal humans in nucleotide excision and in photorepairPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2002Betsy M. Sutherland Background/Aims: Photoreactivation (PR) of cyclobutyl pyrimidine dimers (CPD) in human skin remains controversial. Recently Whitmore et al. (1) reported negative results of experiments using two photorepair light (PRL) sources on UV-irradiated skin of volunteers. However, their PRL sources induced substantial levels of dimers in skin, suggesting that the additional dimers formed could have obscured PR. We met a similar problem of dimer induction by a PRL source. We designed and validated a PRL source of sufficient intensity to catalyse PR, but that did not induce CPD, and used it to measure photorepair in human skin. Methods and Results: Using a solar simulator filtered with three types of UV-filters, we found significant dimer formation in skin, quantified by number average length analysis using electrophoretic gels of isolated skin DNA. To prevent scattered UV from reaching the skin, we interposed shields between the filters and skin, and showed that the UV-filtered/shielded solar simulator system did not induce damage in isolated DNA or in human skin. We exposed skin of seven healthy human volunteers to 302 nm radiation, then to the improved PRL source (control skin areas were kept in the dark for measurement of excision repair). Conclusions: Using a high intensity PRL source that did not induce dimers in skin, we found that three of seven subjects carried out rapid photorepair of dimers; two carried out moderate or slow dimer photorepair, and three did not show detectable photorepair. Excision repair was similarly variable in these volunteers. Subjects with slower excision repair showed rapid photorepair, whereas those with rapid excision generally showed little or no photoreactivation. [source] Randomized Double-blind Placebo Controlled Crossover Study of Acetaminophen, Ibuprofen, Acetaminophen/Hydrocodone, and Placebo for the Relief of Pain From a Standard Painful StimulusACADEMIC EMERGENCY MEDICINE, Issue 9 2009James R. Miner MD Abstract Objectives:, The objective was to compare subjects' change in perceived acute pain from an identical painful stimulus after receiving three separate, commonly used pain medications and placebo. Methods:, This was an institutional review board,approved, randomized, double-blind crossover study of healthy human volunteers. Subjects received 1000 mg of acetaminophen, 800 mg of ibuprofen, the combination of 650 mg of acetaminophen with 10 mg of hydrocodone, or placebo (800 mg of lactose) in a randomized order over four separate occasions each 1 week apart. Prior to receiving the drug on each study day, subjects placed their nondominant hand in a bath of 0°C water for 45 seconds. The bath was divided into two sections; the larger was the reservoir of cooled water monitored at 0°C, and the other half was filled from constant overflow. Water drained from the overflow section into the cooling unit and was then pumped up into the base of the reservoir through a diffusion grid. Subjects completed a 100-mm visual analog scale (VAS) representing perceived pain during the exposure. The cold water exposure and VAS were repeated 1 hour after receiving the study drug, and then subjects were observed for side effects for 4 hours. Data were compared using descriptive statistics, 95% confidence intervals (CIs), and repeated-measures analysis of variance (ANOVA). Results:, Twenty-five subjects were enrolled. The mean VAS preexposure was 56.9 mm (±15.1 mm; range = 5 to 92 mm). The mean decrease in VAS after receiving the study drug for acetaminophen was 10.2% (95% CI = ,1.4 to 20.4), for ibuprofen was ,6.6% (95% CI = ,16.5 to 3.20), for acetaminophen/hydrocodone was 9.5% (95% CI = 1.4 to 20.4), and for placebo was ,6.9% (95% CI = ,15.2 to 1.4). The range in change in pain scores for all agents was ,91.3% to 57.6%. Mild side effects (nausea, dizziness, or somnolence) were reported in 11 subjects (44%) after receiving acetaminophen/hydrocodone; no other side effects were reported. Conclusions:, There was a wide range of changes in pain scores from this identical painful stimulus after receiving the study medications. Acetaminophen and acetaminophen/hydrocodone resulted in a similar decrease in pain (10.2 and 9.5%), while ibuprofen and placebo had a similar lack of effect (,6.6 and ,6.9%). Forty-four percent of subjects receiving acetaminophen/hydrocodone reported mild side effects; no other side effects were seen. In this noninflammatory pain model, the VAS is not able to distinguish differences in pain relief between acetaminophen and acetaminophen/hydrocodone or ibuprofen and placebo. [source] Watercress has No Importance for the Elimination of Ethanol by CYP2E1 InhibitionBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2002Jean-Pierre Desager Since ethanol and its metabolite, acetaldehyde, are CYP2E1 substrates, the influence of watercress on ethanol and acetaldehyde was investigated in healthy human volunteers. According to a randomized cross-over design, ethanol and acetaldehyde pharmacokinetic parameters were determined in 9 persons at 3 occasions: without watercress and after watercress ingestion preceding ethanol consumption from 1 or 10.5 hr, respectively. Ethanol tmax occurred significantly later when watercress was ingested 1 hr before ethanol ingestion. Likewise, acetaldehyde Cmax was significantly higher whereas acetaldehyde AUCs were increased by watercress but not significantly. All other ethanol and acetaldehyde pharmacokinetic parameters were similar between the 3 treatments. In healthy volunteers, no major watercress effect was observed on ethanol clearance but a weak inhibiting effect on acetaldehyde metabolism is possible. Ethanol absorption is also delayed by single ingestion of watercress immediately preceding ethanol consumption. [source] Bioequivalence evaluation of two brands of furosemide 40mg tablets (Salurin and Lasix) in healthy human volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2003Naji Najib Abstract A randomized, two-way, crossover, bioequivalence study was conducted in 24 fasting, healthy, male volunteers to compare two brands of furosemide 40 mg tablets, Salurin (Julphar, UAE) as test and Lasix (Hoechst AG, Germany) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in a joint venture with Al-Mowasah Hospital, Amman, Jordan. One tablet of either formulation was administered with 240 ml of water after a 10 h overnight fast. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested from blood was analysed for furosemide by a validated HPLC method. Various pharmacokinetic parameters including AUC0,t, AUC0,,, Cmax, Tmax, T1/2, and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC0,t, AUC0,,, and Cmax to assess the bioequivalence of the two brands which revealed no significant difference between them, and 90% CI fell within the US FDA accepted bioequivalence range of 80%,125%. Based on these statistical inferences, Salurin was found to be bioequivalent to Lasix. Copyright © 2003 John Wiley & Sons, Ltd. [source] Time dependent pharmacokinetics of albendazole in humanBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2003A. Mirfazaelian Abstract The pharmacokinetics of the main metabolites of albendazole (albendazole sulphoxide (ABZ-SO) and albendazole sulphone (ABZ-SO2)) were studied in 12 healthy human volunteers in a double blind design on the first and last days of oral administration of 800 mg albendazole daily for 15 days. No significant differences were observed in Cmax, Tmax and Vd/F of ABZ-SO, whereas the AUC, AUMC and T1/2 of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. There were also no significant differences in the Cmax, Tmax, Vd/F and T1/2 of ABZ-SO2, whereas the AUC and AUMC of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. These observations suggest time dependent pharmacokinetics of albendazole (observed for ABZ-SO and ABZ-SO2), which was explained on the basis of the induction of enzymes involved in the metabolism of ABZ-SO (albendazole sulphoxide) to metabolites other than albendazole sulphone in multiple dosing. Copyright © 2003 John Wiley & Sons, Ltd. [source] Bioequivalence assessment of Azomycin® (Julphar, UAE) as compared to Zithromax® (Pfizer, USA),two brands of azithromycin,in healthy human volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2001Naji M. Najib Abstract Two studies have been performed to assess the relative bioavailability of Azomycin® (Julphar, UAE) as compared with Zithromax® (Pfizer, USA) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved Azomycin® capsules and the other Azomycin® suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of azithromycin were administered as single dose on two treatment days separated by a 2 weeks washout period. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood, was analysed for azithromycin by HPLC coupled with electrochemical detection. Various pharmacokinetic parameters including AUC0,t, AUC0,,,Cmax, Tmax, T1/2 and Kelm were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC0,t, AUC0,, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratios of these parameters were found within the bioequivalence acceptance range of 80,125%. Based on these statistical inferences it was concluded that Azomycin® capsule is bioequivalent to Zithromax® capsule and Azomycin® suspension is bioequivalent to Zithromax® suspension. Copyright © 2001 John Wiley & Sons, Ltd. [source] An Overview of SR121463, a Selective Non-Peptide Vasopressin V2 Receptor AntagonistCARDIOVASCULAR THERAPEUTICS, Issue 3 2001C. Serradeil-Le Gal ABSTRACT SR121463 is a selective, orally active, non-peptide antagonist of vasopressin (AVP) V2 receptors with powerful aquaretic properties in various animal species and humans. SR121463 belongs to a new class of drugs, called aquaretics, which are capable of inducing free-water excretion without affecting electrolyte balance. SR121463 displays high affinity for animal and human V2 receptors and exhibits a remarkably selective V2 receptor profile. SR121463 and [3H]SR121463 are used, therefore, as selective probes for characterization and labeling of V2 receptors. In various functional studies in vitro, SR121463 behaves as a potent antagonist. It inhibits AVP-stimulated human renal adenylyl cyclase and dDAVP (1-desamino, 8-D arginine-vasopressin)-induced relaxation of rat aorta. SR121463 also behaves as an inverse agonist in cells expressing a constitutively activated human V2 receptor mutant. In vitro, SR1 21463 rescued misfolded V2 AVP receptor mutants by increasing cell surface expression and restoring V2 function. In normally hydrated conscious rats, dogs and monkeys, SR121463, by either i.v. or p.o. administration, induced a dose-dependent aquaresis with no major changes in urinary Na+ and K+ excretion (unlike classical diuretics). In cirrhotic rats with ascites and impaired renal function, a 10-day treatment with SR121463 totally corrected hyponatremia and restored normal urine excretion. In a model of diabetic nephropathy in rats, SR121463 strongly reduced albumin excretion. SR121463 was also effective at extrarenal V2 (or V2 -like) receptors involved in vascular relaxation or clotting factor release in vitro and in vivo. In the rabbit model of ocular hypertension, SR121463 by either single or repeated instillation, decreased intraocular pressure. After acute and chronic administration to rats, dogs or healthy human volunteers, SR121463 was well absorbed and well tolerated. In all species studied the drug produced pronounced aquaresis without any agonist effect. Thus, SR121463 is a potent, orally active and selective antagonist at V2 receptors with powerful aquaretic properties. It is a useful tool for further exploration of function of renal or extrarenal V2 receptors. Pure V2 receptor antagonists are likely to be therapeutically useful in several water-retaining diseases such as hyponatremia, Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH), congestive heart failure, liver cirrhosis, and other disorders possibly mediated by V2 receptors (e.g., glaucoma). [source] | |||||||||||||||||||||||||