Bioequivalence Study of Two Ibuprofen Formulations Administered Intravenously in Healthy Male Volunteers

Abstract

To compare the systemic bioavailability of two ibuprofen formulations, Pedea((R)) (ibuprofen intravenous [IV] formulation) and Imbun((R)) (ibuprofen intramuscular [IM] formulation) in 18 healthy male volunteers. Each subject received a 5 mg/kg dose of ibuprofen base as a short 15-minute IV infusion as the Pedea((R)) ibuprofen IV formulation or as the reference Imbun((R)) IM formulation. Concentrations of R- and S-ibuprofen were measured by a validated HPLC method with a lower limit of quantification of 0.100 microg/mL. A single 5 mg/kg injection of Pedea((R)) was well tolerated. The most frequent adverse event was a mild to moderate burning sensation along the injection vein probably related to the study treatments.The maximum serum concentration (C(max)) of R- and S-ibuprofen ranged from 20 to 35 microg/mL with both formulations. No statistical differences were observed for either C(max) or area under the plasma concentration-time curve (AUC). 90% CIs calculated for C(max) and AUC from time zero to infinity (AUC(infinity)) of R-ibuprofen and S-ibuprofen were included in the bioequivalence range 0.80-1.25. Based on AUC(infinity), the mean (SD) relative bioavailability of Pedea((R)) (ibuprofen IV formulation) versus the Imbun((R)) IM reference formulation was 1.06 (0.17) for R-ibuprofen and 1.05 (0.08) for S-ibuprofen. This study showed that Pedea((R)) (test formulation) is bioequivalent to Imbun((R)) IM (reference formulation) for both R-ibuprofen and S-ibuprofen. The Imbun((R)) IM formulation (lyophilisate) could be replaced by the Pedea((R)) ready-to-use IV solution. Moreover, these results allow a comparison of safety and efficacy data previously generated with either formulation. Consequently, neonatologists, who previously used the IM formulation intravenously for the treatment of patent ductus arteriosus in preterm infants, will now be able to administer the new ready-to-use IV solution of ibuprofen directly.