A simple LC-MS/MS method for pharmacokinetic study of carvedilol and 4/-hydroxyphenyl carvedilol at a low dose.

Background and purpose: The study was aimed at validating a simple, rapid, and low-cost LC-MS/MS method for carvedilol and 4/-hydroxyphenyl carvedilol assay in human plasma. The validated method was applied to investigate the pharmacokinetics after a low dose of 6.25 mg. carvedilol. Experimental approach: In this study, the plasma was extracted by liquid-liquid extraction and evaporated the organic layer to dryness, then both analytes in the residue were reconstituted and detected by LC- MS/MS. The method was validated following the guideline on bioanalytical method validation. Thirty-one healthy volunteers participated in the pharmacokinetic study. After 10 h of fasting, each volunteer received one tablet of 6.25 mg carvedilol orally. Blood samples were collected at 16 prescheduled time points. The plasma samples were analyzed for pharmacokinetics. Findings/Results: The method was linear over a range of 0.050-50.049 ng/mL for carvedilol and 0.050- 10.017 ng/mL for 4/-hydroxyphenyl carvedilol. Crucial validated results reached the requirements of selectivity, accuracy, precision, and stability. Pharmacokinetics of carvedilol and 4/-hydroxyphenyl carvedilol were evaluated which showed Cmax at 21.26 ± 9.23 and 2.42 ± 2.07 ng/mL; AUC0-t 66.95 ± 29.45 and 5.93 ± 3.51 ng.h/mL; AUC0-inf 68.54 ± 30.11 and 6.78 ± 3.49 ng.h/mL; and T1/2 6.30 ± 1.95 and 6.31 ± 6.45 h, respectively. Conclusion and implications: The validated method was able to detect and quantify both analytes in plasma samples and can be applied to the pharmacokinetic study of carvedilol and 4/-hydroxyphenyl carvedilol after receiving carvedilol at 6.25 mg orally.

Pharmacokinetics and bioequivalence of a pregabalin 150-mg capsule in healthy Thai subjects.

OBJECTIVE: The purpose of the study was to evaluate the pharmacokinetics and bioequivalence of pregabalin following administration of a 150-mg capsule of test and reference products. METHOD: The study was designed as a randomized, two-treatment, two-period, two-sequence, single-dose crossover with 1-week washout period between period I and period II dosing. 20 healthy male and female Thai subjects were enrolled in the study. Each subject was in fasted state for ~ 10 hours prior to receiving a single oral 150-mg pregabalin capsule. Serial blood samples were collected at pre-dose until 32 hours after drug administration. Plasma samples were extracted by protein precipitation and derivatized with 4-chloro-7-nitrobenzofurazan. Pregabalin plasma concentrations were determined by HPLC method, and pharmacokinetic parameters were calculated. For bioequivalence assessment, the differences of Cmax, AUC0-t, and AUC0-inf means based on ln-transformed data were assessed by the 90% confidence interval (CI). RESULTS: Pharmacokinetic parameters were determined that test and reference products showed 0.96 ± 0.35 and 1.04 ± 0.96 hours for tmax, 4,594.217 ± 834.195 and 4,568.68 ± 573.963 ng/mL for Cmax, 30,048.150 ± 2,998.920 and 29,315.722 ± 2,747.396 ng×h/mL for AUC0-t, 30,594.210 ± 2,872.317 and 29,831.454 ± 2,688.020 ng×h/mL for AUC0-inf, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-inf for test and reference products were assessed at 95.356 - 104.630%, 99.303 - 105.751%, and 99.373 - 105.788%, respectively. The results were within the acceptance criteria of 80 - 125%. CONCLUSION: Pharmacokinetic parameters of a single oral 150-mg pregabalin capsule in healthy Thai subjects were evaluated and showed rapid absorption. 90% CI for the differences of Cmax, AUC0-t, and AUC0-inf were within the acceptable range of the criteria so that bioequivalence of the test and reference products of pregabalin 150-mg capsule could be concluded.
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Pharmacokinetics and bioequivalence study of irbesartan tablets after a single oral dose of 300 mg in healthy Thai volunteers.

OBJECTIVE: Pharmacokinetics and bioequivalence of 300 mg irbesartan tablets were studied in 26 healthy Thai male volunteers. METHODS: A single oral dose of one 300 mg tablet of the test product and the reference product was given to each volunteer according to a randomized two-way crossover design with 1-week wash out period. Blood samples were collected at predetermined time intervals until 72 hours post dose and irbesartan concentration was quantified with a validated HPLC method. Individual plasma irbesartan concentration-time profile was analyzed for pharmacokinetic parameters. RESULTS: Maximum plasma concentrations (Cmax) of 3,617.19 and 3,295.77 ng/mL for test and reference, respectively, were achieved. Areas under the plasma concentration-time curve; AUC0-t and AUC0-∞ were 15,304.65 and 15,638.90 ng×h/mL for test and 15,389.21 and 15,730.34 ng×h/mL for reference. The median tmax was 1.50 hours and 1.25 hours for test and reference, respectively. Plasma elimination half-lives (t1/2) were 7.35 hours and 8.09 hours for test and reference, respectively. Primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ were tested parametrically by analysis of variance (ANOVA), and it revealed no statistically significant difference (defined as p < 0.05) between the corresponding Cmax, AUC0-t, and AUC0-∞ with respect to sequence, volunteers, period and formulation. The 90% confidence intervals for the ratio of test and reference product of the parameters Cmax, AUC0-t, and AUC0-∞ were within 80 - 125% (100.13 - 121.40% for Cmax, 90.83 - 106.86% for AUC0-t and 91.11 - 106.55% for AUC0-∞). CONCLUSION: The two products were bioequivalent in terms of both rate and extent of drug absorption into systemic circulation.

Pharmacokinetic of gabapentin 600 mg tablet in Thai healthy subjects.

BACKGROUND: Gabapentin is an antiepileptic drug. It is structurally similar to yaminobutyric acid (GABA), which crosses the blood-brain barrier. Gabapentin is absorbed into the blood by the L-amino acid transport system. The oral bioavailability of gabapentin displays dose-dependence. Plasma concentrations ofgabapentin are not directly proportional to dose. Therefore, pharmacokinetic of gabapentin is essential for patients who have to receive gabapentin 600 mg. OBJECTIVE: To investigate the pharmacokinetic of gabapentin 600 mg in Thai healthy subjects. MATERIAL AND METHOD: The present study was performed on 24 healthy Thai male subjects who received a single oral dose of 600 mg gabapentin tablet. Serial blood samples were collected before and to 48 hours after drug administration. Plasma gabapentin concentrations were determined by automated High Performance Liquid Chromatography (HPLC) with UV detector after deproteinized with acetonitrile followed by derivatization with 1-fluoro-2,4-dinitrobenzene. The relevant pharmacokinetic parameters were determined. RESULTS: The mean values of pharmacokinetic parameters (mean +/- SD) were 3.17 +/- 0.80 hour (1.5 to 5.0 hour) for T; 4,853.58 +/- 1,369.67 ng/ml for Cm; 0.11 +/- 0.02 hour for Kel, 6.62 +/- 1.87 hour (4.89 to 11.41 hour) for T1/2; 47,712.88 +/- 12,853.61 ng.hour/ml for AUC0-t, 48,713.20 +/- 12,909.78 ng.hour/ml for AUC0-inf, 5.24 +/- 1.32 L/hour for CI, and 49.28 +/- 15.98 L for Vd. CONCLUSION: The data show the pharmacokinetic parameters of gabapentin 600 mg. These data should be used to support the assignment of therapeutic purposes for patients who have to receive gabapentin 600 mg.