Bioequivalence Study of Two Formulations of Simvastatin 20 mg Tablet in Healthy Filipino Participants under Fasting Conditions: A Randomized, Open-label, Two-way Crossover Study

Abstract

Objectives. Bioequivalence studies provide evidence that generic drugs can produce the same blood levels asthe innovator, suggesting similar efficacy and safety and indicating interchangeability without the need to titratedosing. This study aimed to compare the rate and extent of absorption of two simvastatin 20 mg tablets of Pascual Laboratories, Inc. with two Zocor 20 mg tablets of Merck Sharp & Dohme (I.A.) Corp. in healthy Filipinos. The study also monitored the safety and tolerability of the medications, under the same conditions. Proof of bioequivalence is required by FDA Philippines to establish the interchangeability of generic products and their innovators.Methods. Twenty-four healthy participants were administered with a single oral dose of two 20 mg simvastatintablets under fasting conditions, in a randomized, open-label, blind-endpoint analysis, two-way crossover study,with a washout period of one week. Pharmacokinetic blood sampling was done up to 24 h post-dose. Simvastatin was measured using Liquid Chromatography-Tandem Mass Spectrometry with a validated method. The geometric mean ratios for maximum plasma concentration (Cmax) and area under the plasma-concentration-time curve from time zero to the last observed concentration at time 24 h (AUC0-24) were used for bioequivalence.Results. All 24 participants, 12 males and 12 females, completed the study. Mean age was 24.21 years, mean weight was 58.81 kg, and mean BMI was 23.16 kg/m2. The ratios of Cmax and AUC0-24 were 102.17% (90% CI: 89.19-117.03), and 101.29% (90% CI: 86.87-118.10), respectively, and were both within the bioequivalence limits of 80% to 125%. No adverse event was reported and both formulations were well-tolerated.Conclusion. Simvastatin 20 mg tablet of Pascual Laboratories, Inc. and the innovator Zocor 20 mg tablet arebioequivalent. Single two-tablet doses of both products are safe and well tolerated.