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.

Pharmacokinetic and bioequivalence study of an oral 8 mg dose of rosiglitazone tablets in Thai healthy volunteers.

BACKGROUND: Rosiglitazone maleate is an antihyperglycemic agent in the thiazolidinedione class. It is indicated for the treatment of patients with type 2 diabetes mellitus. A new product of rosiglitazone has been developed. The pharmacokinetic in Thai subjects should be considered and the bioequivalent data of new generic product is required in order to assure the quality and performance. OBJECTIVE: To characterize the pharmacokinetics of rosiglitazone in Thai subjects and compare the bioequivalence of generic product of a single oral 8 mg rosiglitazone tablet with the innovator's product. MATERIAL AND METHOD: The present study was performed in 24 healthy Thai male volunteers. Each received a single oral dose of 8 mg rosiglitazone tablet. Double blind randomized two-way crossover design was used with two weeks washout period between treatments. After drug administration, a serial blood sample was collected over a period of 48 hours. Rosiglitazone plasma level was determined by HPLC with fluorescence detector. The pharmacokinetic parameters were determined by non compartment model. For bioequivalence determination, the difference of Cmax, AUC(0-t) and AUC(0-inf) were analyzed by ANOVA and 90% confidence interval. RESULTS: The mean +/- SD of pharmacokinetic parameters of generic product and the innovator's product were 0.82 +/- 0.52 vs. 1.02 +/- 1.50 hr of Tmax, 796.51 +/- 155.19 vs. 723.48 +/- 134.69 ng/ml of Cmax, 3.94 +/- 0.80 vs. 3.87 +/- 0.77 hr of T1/2, 4,308.43 +/- 1,006.28 vs. 4,135.66 +/- 1,061.96 ng x hr/ml of AUC(0-t), 4,384.65 +/- 1,035.15 vs. 4,183.87 +/- 1,075.39 ng x hr/ml of AUC(0-inf), respectively. The 90% confidence interval of mean difference of Cmax, AUC(0-t) and AUC(0-inf) (log transformed data) of generic product compared to the innovator's product were 98.42-122.18%, 97.28-109.66% and 97.79-110.30%, respectively. They were within the range of the acceptance criteria 80-125%. CONCLUSION: Pharmacokinetic parameters of a single oral dose of 8 mg rosiglitazone tablet were characterized in Thai healthy subjects. These parameters showed that rosiglitazone was rapidly absorbed with a short elimination half-life. The two formulations of rosiglitazone were bioequivalent.

The pharmacokinetics of pioglitazone in Thai healthy subjects.

BACKGROUND: Pioglitazone is a thiazolidinedione compound used in the treatment of type 2 diabetes, metabolized mainly by CYP2C8 and CYP3A4. Due to genetic polymorphisms in CYP2C8, interethnic variability in pharmacokinetics should be considered. OBJECTIVE: To conduct a study on the pharmacokinetics of pioglitazone in Thai subjects. MATERIAL AND METHOD: The present study was performed in 24 Thai male healthy subjects. After an overnight fasting, each subject had a single oral dose of 30 mg pioglitazone tablet. Serial blood samples were collected before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 24 and 48 hours after drug administration. Plasma pioglitazone was determined by automated High Performance Liquid Chromatography (HPLC) with UV detection after deproteinized with acetonitrile. The relevant pharmacokinetic parameters including peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination rate constant (Kel), elimination half-life (T1/2), area under the plasma concentration-time curve (AUC(0-t), AUC(0-inf)), clearance (Cl) and volume of distribution (Vd) were determined. RESULTS: After a single oral dose of 30 mg pioglitazone tablet, the drug was absorbed into systemic circulation with time to maximum concentration (Tmax) at 2.00 +/- 1.61 (0.5-6) hr, and the plasma level reached the maximum concentration (Cmax) of 1.14 +/- 0.29 (0.47-1.63) microg/ml. The AUC was 11.47 +/- 4.77 and 16.69 +/- 7.75 microg x hr/ml for AUC(0-t) and AUC(0-inf) respectively. The elimination rate constant (Kel) of pioglitazone obtained was 0.08 +/- 0.04 hr(-1), whereas the t1/2 was 11.19 +/- 7.38 hrs with the clearance (Cl) of 2.26 +/- 1.22 L/hr. The apparent volume of distribution (Vd) was found to be 30.19 +/- 13.06 L. CONCLUSION: Pharmacokinetic parameters of 30 mg single oral dose of pioglitazone were characterized in Thai subjects. These parameters showed that pioglitazone had a rapid rate of absorption, small volume of distribution and short elimination half-life.

Clinical pharmacokinetic of celecoxib in healthy Thai volunteers.

BACKGROUND: Celecoxib, a nonsteroidal antiinflammatory drug exhibits its antiinflammatory effect by selective inhibition of cyclooxygenase-2 (COX-2) enzyme. Its efficacy has been accepted for the treatment of arthritic pain with superior gastrointestinal side effect profile compared with other conventional NSAIDs. OBJECTIVE: To elucidate clinical pharmacokinetic of celecoxib following an oral dose administration. MATERIAL AND METHOD: Eighteen healthy Thai male volunteers were enrolled in the present study. Their mean age was 20.94 +/- 1.21 years and their mean weight was 63 +/- 5.17 kg. They were orally administered 200 mg celecoxib after an over night fasting, serial blood samples were drawn before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 48 hours after dosing. Plasma celecoxib was analysed by reversed-phase HPLC. RESULTS: Following a 200 mg celecoxib oral administration, the drug was absorbed into the systemic circulation and reach maximum concentration (Tmax) within 2.50 +/- 1.22 hrs by average with the mean peak concentration (Cmax) of 686.83 +/- 211.35 ng/ml. The extent of absorption (area under the curve, AUC) was approximately 5157.12 +/- 1499.46 and 5911.48 +/- 1363.51 ng hr/ml for AUC(0-->t) and AUC(0-->infinity) respectively. The apparent volume of distribution (Vd) was found to be 458.93 +/- 323.28 L/hr. Celecoxib was eliminated after biotransformation and the metabolites were excreted in both urine and feces. The elimination half-life (t(1/2)) of celecoxib appeared to be 8.79 +/- 5.49 hrs with the apparent clearance (CL) of 35.91 +/- 9.85 L. The elimination rate constant for celecoxib obtained from this present study was about 0.11 +/- 0.05 hr(-1). CONCLUSION: Pharmacokinetic parameters following an oral dose of 200 mg celecoxib administration were characterized, including Cmax, Tmax, Vd, kel, CL, AUC. These parameters reflected absorption, distribution, biotransformation and excretion of celecoxib in healthy Thai volunteers.