Single Dose Bioequivalence Study of Two Brands of Olanzapine 10 mg Tablets in Iranian Healthy Volunteers

Abstract

This single dose, randomized, open label, 2-period and crossover study in healthy Iranian adult volunteers was conducted to compare the bioavailability of 2 branded formulations of olanzapine 10 mg tablets. 24 volunteers received one tablet of each olanzapine 10 mg formulation. Drugs were administered after a 12 h overnight fast in each of 2 treatment days which separated by a 2-week washout period. Serial blood samples were collected over a period of 72 h. Plasma was analyzed using a validated high performance liquid chromatography method with ultraviolet detection in the range of 2-24 ng/mL with a lower limit of quantitation of 1.25 ng/mL. A non-compartmental method was employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0-t, AUC0-∞ and T1/2) to test to bioequivalence. Cmax, AUC0-t and AUC0-∞ were used to test the bioequivalence after log-transformation of plasma data. The mean (SD) Cmax, AUC0-t and AUC0-∞ for the test formulation were 15.82 (3.15) ng/mL, 447.19 (100.64) ng.h/L and 570.75 (130.55) ng.h/L respectively. Corresponding values for the test formulation were 15.72 (4.25) ng/mL, 440.37 (98.75) ng.h/mL and 558.66 (129.57) ng.h/mL. For test formulation vs. the reference formulation, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t and AUC0-∞ were 97.6-110.0%, 96.4-109.4% and 97.3-109.2%. In these volunteers, based on the FDA regulatory definition, results from the pharmacokinetic analysis suggested that the test and reference formulations of olanzapine 10 mg tablets were bioequivalent.

The development and validation of a method for quantifying olanzapine in human plasma by liquid chromatography tandem mass spectrometry and its application in a pharmacokinetic study

“…This could contribute to the differences in pharmacokinetic profiles between the ethnic populations . The C max determined in the present study is in accordance with the previously reported Iranian and Egyptian studies …”

“…40 The C max determined in the present study is in accordance with the previously reported Iranian and Egyptian studies. 1,33 The high C max value found in the Asian studies could explain the high number of adverse events in the Thai study. 35 A total of 108 adverse events were reported (50 from the test product and 58 of the reference product); all adverse events were mild and no serious adverse effects were observed.…”

“…We proceeded with a comparison of the pharmacokinetic parameters reported in the literature . Table shows the results of the C max , AUC 0– t , and AUC 0–∞ of studies on subjects of different ethnicities (Chinese, Thai, Iranian, and Egyptian) that were performed on healthy male volunteers (except for the Thai study, which included 12 men and 12 women).…”

“…31 We proceeded with a comparison of the pharmacokinetic parameters reported in the literature. 1,[33][34][35][36] Table 4 shows the results of the C max , AUC 0-t , and AUC 0-∞ of studies on subjects of different ethnicities (Chinese, Thai, Iranian, and Egyptian) that were performed on healthy male volunteers (except for the Thai study, which included 12 men and 12 women). The studies were open-label, randomized, two-period, two-treatment, two-sequence, and 2 9 2 crossover, and were performed under fasting conditions; the plasma levels after the administration of a 10-mg OLZ tablet were determined.…”