A Single-Dose, Randomized

A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions Clinical Therapeutics, Volume 31, Issue 3, March 2009, Pages 600-608 Ahmed H. Elshafeey, Mohamed A. Elsherbiny, Mohsen M. Fathallah Methods: This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions.Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-72, and AUC0-? was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%–125%), as established by the US Food and Drug Administration (FDA).Both the test product (Trademark: Integrol ® [Global Napi Pharma ceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa ® [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0. 67 to 16. 7 ng/mL, with a lower limit of quantitation of 0. 167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Results: Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24. 7 (6. 2) years (range, 19–41 years), mean weight was 73. 4 (6. 7) kg (range, 64–89 kg), and mean height was 174. 25 (4. 6) cm (range, 168–186 cm).Values for Cmax, AUC0-72, AUC0-? Tmax, t1/2, and the terminal disposition rate constant were found to be in agreement with previously reported values. The differences between the 2 products did not reach statistical significance at P ? 0. 05 (90% CIs: Cmax, 101. 82–124. 79; AUC0-72, 93. 36–102. 04; and AUC0-? , 88. 57–101. 77). The test/reference ratio of these parameters was within the acceptance range of the FDA criterion for bioequivalence. Both formulations were apparently well absorbed from the astrointestinal tract (ie, no specific gastrointestinal tract-related adverse events were reported). Conclusions: In this small study in healthy male volunteers, there were no statistically significant differences in any of the calculated pharmacokinetic parameters between the 10-mg test and reference tablets of olanzapine. The 90% CIs for the ratios of mean Cmax, AUC0-72, and AUC0-? were within the range of 80% to 125% (using log-transformed data ), meeting the FDA regulatory criterion for bioequivalence. Both formulations were well tolerated.