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Oral Dosage (oral + dosage)
Selected AbstractsPlasma pharmacokinetics of warfarin enantiomers in catsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000S.A. SMITH The purpose of this study was to determine the dispositions of S-warfarin and R-warfarin in normal cats following intravenous and oral administrations of racemic warfarin. Citrated blood samples were collected from 10 cats prior to and at times 5, 15, and 30 min, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 72, 96, and 120 h following a single intravenous bolus of 0.5 mg/kg of racemic warfarin. After a 21-day washout period, samples were then similarly collected in three groups of four cats for 120 h following oral administration of 0.1, 0.25, and 0.5 mg/kg racemic warfarin. S-warfarin and R-warfarin were detected using a high-performance liquid chromatography assay validated for cat plasma. Drug concentration,time curves were subjected to non-compartmental analysis. Median pharmacokinetic parameters associated with the intravenous administration of 0.5 mg/kg racemic warfarin were as follows: t1/2 (S:28.2, R:18.3 h), area under the plasma concentration,time curve (AUC; S:33.0, R:24.6 h*,g/mL), area under the moment curve (AUMC; S:1889, R:527.8 h*h*,g/mL), and mean residence time (MRT; S:38.7, R:20.9 h). For each parameter, S-warfarin was significantly different from R-warfarin (P<0.05). Warfarin was absorbed rapidly after oral administration, and the dosage did not affect the time to maximum concentration (S:0.87, R:0.75 h). Oral dosage significantly influenced maximum plasma concentration (ng/mL, S:1267, R:1355 at 0.5 mg/kg; S:614.9, R:679.4 at 0.25 mg/kg; S:250.5, R:367.6 at 0.1 mg/kg), AUC (h*,g/mL, S:45.12, R:30.91 at 0.5 mg/kg; S:22.98:, R:18.99 at 0.25 mg/kg; S:3.922, R:3.570 at 0.1 mg/kg) and AUMC (h*h*,g/mL, S:2135, R:1062 at 0.5 mg/kg; S:943.1, R:599.9 at 0.25 mg/kg; S:132.2, R:59.03 at 0.1 mg/kg), but not t1/2 (S:23.5, R:11.6 h) nor MRT (S:26.3, R:13.5 h). Both warfarin enantiomers were highly (>96.5%) protein-bound. Quantitation of the warfarin content in commercially available tablets indicated an unequal distribution of the drug throughout the tablet. [source] Recommended dietary allowance for vitamin C in the United States is also applicable to a population of young Japanese womenJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2004Hiroshi Ihara Abstract The recommended dietary allowance (RDA) for ascorbic acid (AA) in Canada and the United States has been set for several years at 75 mg/day for women 19,30 years old. Recently this level was questioned, and an increase to 90 mg/day was suggested. For Japanese women in the same age group, we found that the RDA for AA is currently 100 mg/day. Our goal was to determine which RDA is sufficient for maintaining a serum concentration of AA in young Japanese women above the lower reference limit of 7.0 mg/L. We measured serum AA concentrations by an ascorbate oxidase method in 176 healthy Japanese women (19,26 years old). We also performed an ROC analysis to estimate the optimal cutoff value for oral dosage to distinguish individuals with hypovitaminosis-C (<7.0 mg/L) from those with a normal serum AA. We evaluated the Japanese RDA using the 75 or 90 mg/day U.S. RDA and the weight ratio between Japanese and U.S. women, and discovered that the RDA value ranged between 66 and 79 mg/day. From the ROC analysis, we found that the optimal daily dosage of AA is approximately 75 mg/day. This value gave the highest efficiency, sensitivity, negative predictive value, and positive likelihood ratio, and the lowest negative likelihood ratio. Therefore, an RDA of 100 mg/day may be unnecessarily high for young Japanese women. J. Clin. Lab. Anal. 18:305,308, 2004. © 2004 Wiley-Liss, Inc. [source] Effects of Dietary Recombinant Bovine Somatotropin Levels on Growth, Plasma Recombinant Bovine Somatotropin Concentrations, and Body Composition of Juvenile Korean Rockfish, Sebastes schlegeliJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 2 2007Gwangyeol Yoo This experiment was conducted to study the effects of the graded recombinant bovine somatotropin (rBST) levels on growth, plasma rBST concentrations, and body composition of Korean rockfish, Sebastes schlegeli, and to estimate the optimum oral dosage of rBST. Seven experimental diets were formulated to be isonitrogenous and isocaloric and to contain 49.0% crude protein and 16.7 kJ available energy/g, with 0, 5, 10, 15, 20, 25, or 50 mg rBST/kg body weight (BW)/wk (rBST0, rBST5, rBST10, rBST15, rBST20, rBST25, and rBST50, respectively). After the feeding trial, fish fed all the diets supplemented with rBST showed higher weight gain (WG), feed efficiency (FE), specific growth rate (SGR), and protein efficiency ratio (PER) than those fed the rBST0 diet (P < 0.05). WG of fish fed rBST15, rBST20, rBST25, and rBST50 diets was significantly higher than that of fish fed rBST0 and rBST5 diets (P < 0.05); however, there were no significant differences among fish fed rBST10, rBST15, rBST20, rBST25, and rBST50 diets. FE of fish fed rBST15 and rBST20 diets was significantly higher than that of fish fed rBST0, rBST5, rBST10, and rBST50 diets, and fish fed rBST10, rBST25, and rBST50 diets had significantly higher FE than those fed rBST0 and rBST5 diets (P < 0.05). SGR of fish fed all the diets supplemented with rBST was significantly higher than that of fish fed rBST0 diet (P < 0.05); however, there were no significant differences among fish fed all the diets supplemented with rBST. PER of fish fed rBST15 and rBST20 diets was significantly higher than that of fish fed rBST0, rBST5, and rBST50 diets, and fish fed rBST10, rBST25, and rBST50 diets had significantly higher PER than those fed rBST0 and rBST5 diets (P < 0.05). Whole-body protein of fish fed rBST15 diet was significantly higher than that of fish fed rBST0, rBST5, and rBST10 diets (P < 0.05); however, there were no significant differences among fish fed rBST15, rBST20, rBST25, and rBST50 diets. Plasma rBST concentrations of fish fed all the diets began to rise at 3 h after oral administration of rBST; the maximum plasma rBST concentration peaked at 12 h and returned to the basal level at 24 h. Broken-line model analyses of WG and FE were 12.8 and 13.2 mg rBST/kg BW/wk, respectively. These results indicated that the optimum oral dosage could be greater than 12.8 mg rBST/kg BW/wk but less than 13.2 mg rBST/kg BW/wk in juvenile Korean rockfish. [source] Determination of acyclovir in horse plasma and body fluids by high-performance liquid chromatography combined with fluorescence detection and heated electrospray ionization tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 2 2009A. Maes Abstract Two methods are presented for the determination of ,respectively' the plasma protein unbound and total concentration of acyclovir in horse plasma and body fluids: first, a liquid,liquid extraction was performed on plasma, combined with HPLC-fluorescence detection for the total plasma concentration; second a more sensitive method using high-performance liquid chromatography combined with heated electrospray ionization tandem mass spectrometry (LC-HESI-MS/MS) was described for plasma and for body fluids analysis. To obtain the unbound concentration of acyclovir in plasma, a simple deproteinization step using a Microcon® filter was performed. Ganciclovir was used as an internal standard. Analysis was carried out on an Inertsil 5 ODS-3 column for the HPLC-fluorescence method. For the LC-HESI-MS/MS method a PLRP-S column was used. The limit of quantification (LOQ) for the total concentration was set at 50 and 2 ng mL,1 for the HPLC-fluorescence method and the LC-HESI-MS/MS method, respectively. The limit of quantification for the unbound concentration was set at 5 ng mL,1 and at 2 ng mL,1 for body fluids. The methods were successfully used to perform pharmacokinetic and clinical studies in horses after intravenous and oral dosage of acyclovir and its prodrug valacyclovir. Copyright © 2008 John Wiley & Sons, Ltd. [source] Determination of secnidazole in human plasma by high-performance liquid chromatography with UV detection and its application to the bioequivalence studiesBIOMEDICAL CHROMATOGRAPHY, Issue 3 2007Xiaoyu Li Abstract A simple, accurate, precise and sensitive HPLC-UV method was developed for the determination of secnidazole in human plasma. Secnidazole and tinidazole (IS) were extracted from 0.2 mL of human plasma by ethyl acetate. Secnidazole was then separated by HPLC on a Diamond C18 column and quantified by ultraviolet detection at 319 nm. The mobile phase consisted of acetonitrile,aqueous 5 mm sodium acetate (30:70, v/v) containing of 0.1% acetic acid adjusted to pH 4.0, and the flow rate was 1.0 mL/min. The low limit of quantification was 0.1 µg/mL. The method was linear over the concentration range 0.1,25.0 µg/mL (R2 = 1.000). The recovery of secnidazole from human plasma ranged from 76.5 to 89.1%. Inter- and intra-assay precision ranged from 3.3 to 10.7%. Secnidazole in plasma was stable when stored at ambient temperature for 8 h, at ,20°C for 2 weeks and at ,20°C for three freeze,thaw cycles. The developed method was successfully applied to the pharmacokinetic and bioequivalence studies between test and reference secnidazole tablets following a single 500 mg oral dosage to 20 healthy volunteers of both genders. Pharmacokinetics parameters Tmax, Cmax, AUC0,t, AUC0,,, T1/2 were determined of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. It was concluded that the two secnidazole preparations are bioequivalence and may be used interchangeably. Copyright © 2007 John Wiley & Sons, Ltd. [source] Fertility control: Oral versus self-administered vaginal misoprostol at home before surgical termination of pregnancy: a randomised controlled trialBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2006Kevin Sunde Oppegaard Objective, To compare the impact of 400 ,g oral versus self-administered vaginal misoprostol at home on pre-operative cervical priming in both primigravid and multigravid women prior to first trimester surgical abortion. Design, Randomised controlled trial. Setting, Norwegian University Teaching Hospital. Sample, Three hundred and thirty-eight women undergoing surgical abortion between 7 and 12 weeks of gestation. Methods, The women were randomised to either 400 ,g of oral misoprostol the evening before or 400-,g of self-administered vaginal misoprostol at home the same day as vacuum aspiration. Main outcome measures, Pre-operative cervical dilatation, complications and acceptability. Results, The median cervical dilatation was 6.2 mm (range 0,11 mm) for the women in the 400 ,g oral misoprostol and 6.5 mm (range 0,11 mm) in the 400-,g vaginal misoprostol groups. The median pre-operative dilatation was larger in multigravidae (6.4 and 6.7 mm for the oral and vaginal routes, respectively) than in primigravidae (5.8 and 6.0 mm, respectively). In primigravidae, 19% achieved a pre-operative dilatation of ,7 mm, with no significant difference between oral and vaginal dosage. In multigravidae, 52% achieved a pre-operative dilatation of ,7 mm with vaginal dosage, compared with 36% with oral dosage (P= 0.03). There was no difference between non-immigrant versus immigrant women in pre-operative cervical dilatation. The 400-,g oral dosage group had a higher risk of bleeding, compared with the group receiving 400-,g vaginal misoprostol [odds ratio (OR) = 10.4; confidence interval (CI) 5.2,20.8]. There was no difference between non-immigrant and immigrant women in acceptability of self-administered vaginal misoprostol; almost all women found this administration route acceptable. Complications were minor and were distributed equally between the two dosage groups. Conclusions, The vaginal route will result in a satisfactory dilatation in about half of multigravidae but is much less effective in primigravidae. The oral route does not lead to satisfactory dilatation in either group and is associated with a higher occurrence of pre-operative bleeding. Self-administered vaginal misoprostol at home is highly acceptable. [source] The effect of ascorbate on minor recurrent aphthous stomatitisACTA PAEDIATRICA, Issue 3 2010K Yasui Abstract Aim:, Minor recurrent aphthous stomatitis (MRAS) is a common, painful and inflammatory ailment of the oral cavity with juvenile onset and unknown aetiology. The purpose of this study was to evaluate the potential of ascorbate (vitamin C) to reduce the frequency of MRAS and severity of pain. Patients and methods:, Sixteen MRAS patients (9 boys and 7 girls: mean age, 12.0 ± 2.4 years old) were assigned to take an oral dosage of 2000 mg/m2/day ascorbate. Subjects:, Their baseline frequency of outbreaks and the level of pains were compared during the treatment; in addition, a crossover clinical trial was performed. Polymorphonuclear leucocytes play a role in the pathogenesis, and then superoxide anion production was evaluated in prior to ascorbate treatment. Results:, The data indicated a statistically significant 50% reduction in oral ulcer outbreaks and a decline of pain level. Neutrophils were primed for superoxide anion production in the patients with MRAS. Conclusion:, Ascorbate may modulate the generation of reactive oxygen species and augment neutrophil apoptosis, which could prevent neutrophil-mediated inflammation. Ascorbate seems to be effective, but the findings of our study were preliminary and it should be re-evaluated with a larger randomized controlled clinical trials. [source] A physiologically based pharmacokinetic model for endosulfan in the male Sprague-Dawley ratsENVIRONMENTAL TOXICOLOGY, Issue 5 2006Melissa P. L. Chan Abstract Endosulfan, an organochlorine (OC) insecticide belonging to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. To date, no physiologically based pharmacokinetic (PBPK) model has been located for endosulfan in animal species and humans. The estimation by a mathematical model is essential since information on humans can scarcely be obtained experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of 14C-Endosulfan to male Sprague-Dawley rats. The model was parameterized by using reference physiological parameter values and partition coefficients that were determined in the experiment and optimized by manual adjustment until the best visual fit of the simulations with the experimental data were observed. The model was verified by simulating the disposition of 14C-Endosulfan in vivo after single and multiple oral dosages and comparing simulated results with experimental results. The model was further verified by using experimental data retrieved from the literature. The present model could reasonably predict target tissue dosimetries in rats. Simulation with three-time repeated administration of 14C-Endosulfan and experimental data retrieved from the literature by the constructed model fitted fairly well with the experimental results; thus suggesting that the newly developed PBPK model was developed. Sensitivity analyses were used to determine those input parameters with the greatest influence on endosulfan tissue concentrations. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 464,478, 2006. [source] Inhibitors of the Na+/H+ Exchanger Cannot Prevent Atrial Electrical Remodeling in the GoatJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2004YURI BLAAUW M.D. Introduction: It has been suggested that blockade of the Na+/H+ exchanger (NHE1) can prevent atrial fibrillation (AF)-induced electrical remodeling and the development of AF. Methods and Results: AF was maintained by burst pacing in 10 chronically instrumented conscious goats. Intravenous and oral dosages of two NHE1 blockers (EMD87580 and EMD125021) resulted in plasma levels several magnitudes higher than required for effective NHE1 blockade. Shortening of atrial refractoriness immediately after 5 minutes of AF was not prevented by NHE1 blockade. In remodeled atria, increasing dosages of EMD87580 and EMD125021 did not reverse shortening of the atrial refractory period or reduce the duration of AF episodes. The cycle length during persistent AF also was not affected. Oral pretreatment with EMD87580 (8 mg/kg bid) starting 3 days before AF could not prevent electrical remodeling. After 24 and 48 hours of remodeling, the duration of AF paroxysms was 47 ± 32 seconds and 135 ± 63 seconds compared to 56 ± 17 seconds and 136 ± 52 seconds in placebo-treated animals (P > 0.8), respectively. Conclusion: In the goat model of AF, the Na+/H+ exchanger inhibitors EMD87580 and EMD125021 did not prevent or revert AF-induced electrical remodeling. This indicates that activation of the Na+/H+ exchanger is not involved in the intracellular pathways of electrical remodeling. This does not support the suggestion that blockers of the Na+/H+ exchanger may be beneficial for prevention and treatment of AF. (J Cardiovasc Electrophysiol, Vol. 15, pp. 440-446, April 2004) [source] Oral, colonic-release low-molecular-weight heparin: an initial open study of Parnaparin-MMX for the treatment of mild-to-moderate left-sided ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008L. PASTORELLI Summary Background, Efficacy of heparin and low-molecular-weight heparins (LMWHs) in inflammatory bowel disease (IBD) treatment has been suggested. The multimatrix oral formulation MMX releases active drugs in the colon, avoiding systemic absorption. Parnaparin sodium is the LMWH chosen to be carried in the MMX formulation. Aim, To assess the safety of three different oral dosages (70, 140 and 210 mg once daily) of Parnaparin-MMX (CB-01-05) in left-sided ulcerative colitis (UC). Methods, Left-sided UC patients, with a mild-to-moderate relapse were enrolled. All patients received Parnaparin-MMX for 8 weeks. Clinical Activity Index (CAI), Disease Activity Index (DAI), Endoscopic Activity Index and IBD-QoL were assessed throughout the study. A strict clinical and laboratory follow-up, including assessment of anti-factor Xa activity, was performed. Clinical remission was defined as CAI <4. Results, Ten UC patients were enrolled. One patient retired for clinical deterioration. No relevant side effects, including either interference with haemostasis parameters or increased bleeding, were observed. At the end of the treatment, seven patients (70%) were in clinical remission, only one achieving endoscopic healing. Mean final CAI, DAI and IBD-QoL scores were significantly improved from baseline. Conclusions, Parnaparin-MMX appears to be a safe treatment option in mild-to-moderate UC. Controlled studies are warranted. [source] In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humansBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2006Yuji Mano Abstract It was reported that the plasma concentration of indomethacin was increased with concomitant oral dosages of diflunisal in humans. Both indomethacin and diflunisal are glucuronidated in humans. The effects of diflunisal on the indomethacin glucuronidation were thus investigated in vitro using human liver microsomes (HLM) and human intestine microsomes (HIM) in order to assess the drug,drug interaction. The glucuronidation of indomethacin in HLM showed atypical kinetics with Km and Ksi values of 210 and 89.5 µM, respectively, while HIM exhibited Michaelis,Menten kinetics with a Km value of 17.4 µM. Diflunisal inhibited the indomethacin glucuronidation in HLM with IC50 values ranging from 100 to 231 µM. In HIM, inhibition of the indomethacin glucuronidation by diflunisal was more potent with IC50 values of 15.2,48.7 µM. When the clinical dose of diflunisal (250 mg b.i.d.) is taken into consideration, it is expected that the diflunisal concentration in the intestine would be higher than the IC50 values for indomethacin glucuronidation in the intestine. These findings suggest that the clinical drug,drug interaction between diflunisal and indomethacin may be at least partly attributable to the inhibition of indomethacin glucuronidation by diflunisal in the intestine. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||