The study was conducted to find out whether the bioavailability of a 500 mg azithromycin (CAS 83905-01-5) tablet (Zycin, test) was equivalent to that of a reference formulation. The pharmacokinetic parameters assessed in this study were the area under the plasma concentration-time curve from time zero to 120 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (tmax), and the elimination half-life (t1/2). This was a randomized, single blind, two-period, cross-over study which included 18 healthy adult male and female subjects under fasting conditions. In each of the two study periods (separated by a washout of two weeks) a single dose of test or reference drug was administered. Blood samples were taken up to 120 h post dose, the plasma was separated and the concentrations of azithromycin were determined by a LC-MS/MS method. In this study, the mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the test drug were 4967.49 ng x h x mL(-1), 5871.74 ng x h x mL(-1), 412.14 ng/mL, and 51.32 h, respectively. The mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the reference drug were 4276.75 ng x h x mL(-1), 5578.12 ng x h x mL(-1), 419.89 ng/mL, and 51.23 h, respectively. The median tmax of he test drug and reference drug were 3.0 h and 2.0 h, respectively. The geometric mean ratios (90% CI) of the test drug/reference drug for azithromycin were 101.56% (86.61-119.08%) for AUCt, 101.27% (84.97-120.70%) for AUCinf, and 97.78% (84.50-113.16%) for Cmax. Based on this study, it was concluded that the two azithromycin tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.

IntroductionThe present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations).Materials and methodsThis study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7), using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week), a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC) from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax), time to achieve the Cmax, and the elimination half-life.ResultsThe geometric mean ratios (90% confidence interval) of the test drug/reference drug for candesartan were 100.92% (92.15%–110.52%) for the AUC from 0 hours to 24 hours, 100.24% (92.24%–108.95%) for the AUC from time zero to infinity, and 106.71% (93.20%–122.18%) for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05). The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study.ConclusionIt was concluded that the two candesartan tablet formulations (the test and reference product) were bioequivalent.

BackgroundThe current study was conducted to find out whether two oral preparations of 300 mg gabapentin (the test and reference capsules) were bioequivalent.Subjects and methodsThis was a randomized, single-blind, crossover study under fasting condition, with a 7-day washout period, which included 37 healthy adult male and female subjects. After an overnight fast, subjects were given, orally, one capsule of the test drug or of the reference drug. Blood samples were drawn immediately before taking the drug, then at 20 and 40 minutes, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, and 24 hours after dosing, to evaluate pharmacokinetic parameters of the single dose administration, ie, the area under the plasma concentration–time curve (AUC) from time zero to 24 hours (AUCt), AUC from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve Cmax (tmax), and the elimination half-life (t1/2). The plasma concentrations of gabapentin were determined using validated high-performance liquid chromatography with ultraviolet detection.ResultsThe geometric mean ratios (90% confidence interval) of the test drug/reference drug for gabapentin were 103.15% (90.38%–117.72%) for AUCt, 103.53% (90.78%–118.07%) for AUCinf, and 108.06% (96.32%–121.24%) for Cmax. The differences in tmax and t1/2 values between the test and reference drug products for gabapentin were not statistically significant. Light-headedness, nausea, and headache were encountered during the study, but they were all mild and well tolerated. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of gabapentin were within the acceptance range for bioequivalence.ConclusionThe two preparations of gabapentin 300 mg capsule were bioequivalent, thus both can be used interchangeably in the clinical setting.

The bioequivalence of two capsule formulations containing 100 mg minocycline was assessed in 12 healthy adult male and female volunteers in a crossover, randomized, single-blind study. The participating volunteers were required to fast overnight and in the next morning and were given orally one capsule of the test drug (Acnez) or one capsule of the reference drug. Blood samples were drawn immediately before taking the drug (control), and at 0.33, 0.67, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 h after drug administration. One week after the first drug administration (washout period), the procedure was repeated using the alternate drug. Plasma concentrations of the drug were determined by high performance liquid chromatography method with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 60 h (AUC(t)), area under the plasma concentration-time curve from time zero to infinity (AUC(inf)), the peak plasma concentration of the drug (C(max)), time needed to achieve the peak plasma concentration (t(max)), and the elimination half life (t1/2). The mean AUC(t), AUC(inf), C(max), and t were 18038.55 ng x h x mL(-1), 19648.21 ng x h x mL(-1), 1076.01 ng x mL(-1), and 17.33 h, respectively, for the test drug and 17979.43 ng x h x mL(-1), 19639.78 ng x h x mL(-1), 1095.97 ng x mL(-1), and 16.44 h, respectively, for the reference drug. The median (range) of t(max) of the test drug and reference drug were 2.0 (1.0-4.0) h and 2.0 (0.67-4.0) h, respectively. The geometric mean ratios of the test drug/the reference drug for AUC(t), AUC(inf), and C(max) were 98.27% 98.30%, and 97.31%, respectively. The 90% confidence intervals (CIs) were 89.26-108.19% for AUC(t), 89.95-107.41% for AUC(inf), and 89.55-105.73% for C(max). Using Wilcoxon matched-pairs test on the original data, there was no statistically significant difference found between the test and the reference drug products for t(max), values. It can be concluded that the two minocycline capsules (test drug and reference drug) are bioequivalent in terms of the rate and extent of absorption.

DLBS1033 given at the dose of 490 mg 3 times daily was safe and tolerable in healthy adults.