生物等效性和生物利用度杂志

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Assessment of Bioequivalence of Two Tramadol Hydrochloride 100 mg Extended-Release Tablet Formulations in Healthy Thai Volunteer

Vipada Khaowroongrueng, Wiwat Supasena, Polsak Teerawonganan, Ekawan Yoosakul, Lalinthip Saeaue, Busarat Karachot, Isariya Techatanawat, Archawin Rojanawiwat, Praphassorn Surawattanawan

Tramadol hydrochloride 100 mg extended-release tablets is available as the registered trademark, Tramal^® retard in Thailand to reduce a dosing frequency for the treatment of moderate to severe pain. The Government Pharmaceutical Organization had developed the generic tramadol hydrochloride 100 mg extended-release tablets (Tramadol retard GPO^®) to serve as an alternative product which is more accessible and affordable without compromising quality. Two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions were conducted in healthy Thai volunteers using a comparative randomized, two-way crossover, open-label design to demonstrate the equivalence in bio pharmaceutics quality between two tramadol formulations. Tramadol plasma concentrations were quantified using a validated liquid chromatography-mass spectrometry method. The 90% confidence intervals for the geometric least squares mean ratios of log-transformed AUC_0-tlast, AUC_0-∞ and C_max for the single-dose studies and log-transformed AUC _0-τ,ss, C_τ,ss and C _max,ssfor the multiple-dose study were within 80.00%-125.00% of bioequivalence criteria. The analysis of variance did not show significant effect of the formulation on the primary pharmacokinetic parameters. Wilcoxon signed-rank test also showed no significant difference in median t_max between two formulations in any studies. Bioequivalence between the test and reference products was concluded based on insignificant difference in terms of rate and extent of absorption.