Evaluation of Pharmacokinetics and Safety with Bioequivalence of Ibuprofen Sustained-Release Capsules of Two Formulations, in Chinese Healthy Volunteers: Bioequivalence Study

Abstract

Purpose: Ibuprofen is the first of the nonsteroidal anti-inflammatory drug (NSAID) to be used in the clinic. Our aim was to explore the pharmacokinetics (PK), bioequivalence, food effect, and safety of oral ibuprofen sustained-release capsules by two sponsors in healthy volunteers (HVs). Methods: Two separate randomized, open-label, single-dose, crossover-design studies were conducted: a fasting study (n = 24) and a fed study (n = 24). In each study, HVs were 1:1 divided into two groups (T-R and R-T) and received 0.3-g/capsule ibuprofen with a 3-day washout. The plasma was collected for up to 24 hours at the time point after dosing on Day 1/Day 4. The plasma concentrations of ibuprofen were measured using an HPLC-MS/MS method, and PK parameters were determined by noncompartmental methods. Results: Forty-eight healthy volunteers were enrolled. In fasting subjects, the maximum plasma concentration (Cmax, mean ± SD) was 14.86±3.19 μg/mL at 5.0 (4.0, 7.0) hours (median [min, max]) for sponsor T, and 13.88±2.60 μg/mL at 4.5 (3.0, 8.0) hours for sponsor R. In fed subjects, Cmax was 21.31±4.08 μg/mL at 5.6 (4.3, 10.0) hours for sponsor T, and 19.77±3.36 μg/mL at 6.0 (2.0, 8.0) hours for sponsor R. All 90% confidence intervals (CIs) for Cmax, AUC0-t, and AUC0-∞ were within the bioequivalence bounds (80–125%) both fasting and fed studies. Conclusion: Ibuprofen is well tolerated and has a favorable safety profile. In both fasting and fed study, there were no serious AEs, or AEs leading to withdrawal. Bioequivalence is achieved under fasting and fed conditions, supporting the demonstration of biosimilarity.