Pharmacokinetic Comparison of Controlled- and Immediate-Release Formulations of Dexibuprofen after Single and Multiple Oral Doses in Fasting Healthy Male Korean Volunteers

Abstract

Background Dexibuprofen is a pure S(+)-enantiomer product of racemic ibuprofen. A new extended-release form of dexibuprofen has recently been developed. Objective We aimed to compare pharmacokinetic characteristics of controlled-release (CR) and immediate-release (IR) formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers. Methods Both single- and multiple-dose studies used an open-label, randomized, 2-way, crossover design. In the single-dose study, 24 subjects were administered a 600-mg CR or 300-mg IR formulation. In the multiple-dose study, 24 subjects were administered a 600-mg CR formulation q12h or 300-mg IR formulation q6h. Pharmacokinetic parameters of dexibuprofen were determined by noncompartmental analysis. Results All formulations used in the single- and multiple-dose studies were well tolerated, and there were no severe adverse events. In the single-dose study, the mean (SD) AUC 0–t was 155.60 (40.94) μg/h/mL for the CR formulation and 161.11 (37.50) μg/h/mL for the IR formulation; the mean (SD) C max values were 22.71 (6.64) and 23.77 (4.91) μg/mL, respectively; and the median T max values were 2.01 hours and 2.00 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.96 (0.92–1.00) for AUC 0–t and 1.00 (0.87–1.14) for C max. In the multiple-dose study, the mean (SD) AUC 0–τ values for CR and IR were 129.70 (23.72) μg/h/mL and 150.04 (27.09) μg/h/mL, respectively; the mean (SD) C max,ss values were 24.51 (5.12) and 21.69 (5.21) μg/mL, respectively; and the median T max.ss values were 2.51 hours and 5.25 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.86 (0.81–0.91) for AUC 0–τ and 1.13 (1.03–1.24) for C max. Conclusions The pharmacokinetic parameters of single and multiple administrations of dexibuprofen did not differ for the IR and CR formulations in this small, selected group of healthy male Korean subjects. Both formulations were well tolerated.