Determination of Pharmacokinetics of Flurbiprofen in Pakistani Population Using Modified HPLC Method

Abstract

Pharmacokinetics of flurbiprofen has been studied in different populations, especially in Caucasian. However, there are very few studies reported from Eastern part of world. Previous studies suggested that genetic and environmental factors may cause inter-individual differences in flurbiprofen disposition, so we investigated the pharmacokinetics of flurbiprofen in Pakistani subjects. A single oral dose of 100 mg of flurbiprofen was administered to 22 healthy male Pakistani adults after overnight fasting for 10 h. Periodical blood sampling was done at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h after dosing. Plasma concentration of flurbiprofen was determined by a modified high-performance liquid chromatography method, which was simple, sensitive, less time consuming and economical with ordinary internal standard. The method was validated according to ICH guidelines and was found to be sensitive, accurate and precise. The pharmacokinetic parameters observed in Pakistani subjects when compared with other populations (USA, UK, Canadian, French, and Indian) did not show considerable ethnic differences. However, one subject's data was suggestive of being poor metabolizer of flurbiprofen which supports the presence of CYP2C9 polymorphism contributing to inter-individual differences in flurbiprofen disposition. Pharmacogenomic studies are needed to verify this hypothesis.