Chiral Drug Ibuprofen In Vivo Pharmacokinetic Studies

Ibuprofen is a 2-arylpropionic acid marketed as a non-steroidal antiinflamatory drug (NSAID) and is readily available in many dosage forms. The mode of action of the ibuprofen is via inhibition of the cyclooxygenase-mediated transformation of arachidonic acid to thromboxane and the various prostaglandins. It has two enantiomers whose pharmacological activities were significantly different. Although the S(+)-enantiomer of ibuprofen is the eutomer with respect to inhibition of prostaglandin formation, the marketed products containing ibuprofen are almost all supplied as the racemate. The R(-)-enantiomer, the distomer of ibuprofen, has been reported undergo unidirectional conversion of to the S(+)-enantiomer via formation of the acyl CoA thioester of ibuprofen.We investigated the difference of the pharmacokinetic properties after oral administration of conventional granules and Fenbid. Because of the existence of the chiral inversion, the concentration of S(+)-ibuprofen was greater than that of R(+)-ibuprofen after oral administration of two forms. And the ratio of S/R AUC after oral administration of conventional granules and Fenbid were 1.85±0.49,1.78±0.61, respectively, and they were greater than that after intravenous administration (1.36±0.53), it demonstrated that it is possible that the presystemic inversion of ibuprofen was occurred following oral administration. The chiral inversion kinetics of ibuprofen was also evaluated after intraduodenal administration of racemic ibuprofen in conventional granules form and Fenbid compared with intravenous administration in rabbits. The AUC ratios of the S(+)- and R(-)-enantiomers remained almost constant values with time up to 2h after administration of Fenbid, while those after administration of the granules increased with time. R(-)-enantiomer to S(+)-enantiomer inversion ratios after intraduodenal administration of the granules form and Fenbid, and after intravenous injection were calculated to be 1.63,1.94 and 1.19, respectively, indicating that pharmacological effects may depend on the absorption rate in rabbits.The potential interaction between two ibuprofen enantiomers was studied after...