Bioequivalence Study of 10 mg Olanzapine Tablets in Healthy Thai Volunteers

Abstract

Objective: The purpose of this study was to compare the bioequivalence of 10 mg tablets of olanzapine between a generic drug (Olapin ®-10; Unison Laboratories Co., Ltd., Thailand) and a reference drug (Zyprexa ® ,Eli Lilly, England) in healthy volunteers. Subjects and methods: A single dose, randomized, 2-period, 2-sequence, crossover study was conducted in 24 healthy Thai male and female volunteers. Each volunteer received a 10 mg tablet of the reference or test drug under fasting condition with a washout period of at least 21 days. Blood samples were obtained at pre-dose and at various time points up to 120 hours after dosing. Olanzapine plasma concentrations were quantified by a validated method employing liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results: 24 volunteers completed both treatment periods. The geometric mean ratios (GMR) (test/reference) between the two formulations of olanzapine were 95.76% (90%CI, 88.55-103.55%) for C max ; 103.77% (97.49-110.46%) for AUC 0-120 ; and 104.39% (98.20-110.98%) for AUC 0-∞(obs). There was no statistical difference of the Tmax between the two formulations (p>0.05). One hundred and eight adverse events were reported from both formulations. Most of the adverse events were judged to be mild in intensity and did not require additional medical treatment. Conclusion: No significant difference in the analysed pharmacokinetic parameters was found between the two formulations of 10 mg olanzapine in the healthy Thai volunteers. The 90%CI of GMR of the pharmacokinetic parameters was entirely within the equivalence criteria (80-125%). Therefore, it can be concluded that this two olanzapine tablet formulations were considered bioequivalent.

Effect of Food on the Pharmacokinetics of a Combination of Olanzapine and Samidorphan

“…The AE profile was consistent with that observed for OLZ/SAM in healthy subjects . Syncope was reported in 4 subjects, which is consistent with AE reports in studies of OLZ treatment in healthy subjects …”

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

“…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.…”

“…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. 35 In contrast, the current study showed 68 adverse events (33 from the test product and 35 from the reference product).…”

“…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. 35 In contrast, the current study showed 68 adverse events (33 from the test product and 35 from the reference product). The AUC 0-t was not evaluated because different sample collection times were used.…”