Bioequivalence of diclofenac injection formulations assessed in Korean males.

Author(s): Zhu X, Shin WG

Affiliation(s): Clinical Pharmacy, College of Pharmacy, Seoul National University, South Korea.

Publication date & source: 2005-11, Int J Clin Pharmacol Ther., 43(11):546-50.

Publication type: Randomized Controlled Trial

A bioequivalence study of diclofenac injection (test formulation (diclofenac potassium): HANA, reference formulation (diclofenac sodium): Shinpoong) was conducted in 18 healthy male Korean volunteers who received each medicine at a dose of 75 mg in a 2 x 2 crossover study. There was a one-week washout period between the doses. Plasma concentrations of diclofenac were monitored by high-performance liquid chromatography over a period of 24 hours after the i.m. injection. AUC0-24 (the area under the plasma concentration-time curve from time 0-24 hours) was calculated by the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-24 and Cmax, and non-transformed tmax. There were no significant differences between the medications in AUC0-24 and Cmax. The point estimates and 90% confidence intervals for AUC0-24 (parametric) and Cmax (parametric) were 0.973 (0.8971 to 1.0557) and 0.993 (0.9452-1.0451), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value for tmax was 0.75 (0.00 to 1.00). Moreover, the modified Pitman-Morgan's adjusted F-test indicated that the bioavailabilities of diclofenac in the two medications were comparable regarding intra- and interindividual variability. Therefore, these results indicate that the two medications of diclofenac are bioequivalent and, thus, may be prescribed interchangeably.