Pharmacokinetic interaction of ibuprofen enantiomers in rabbits

Abstract

Abstract The potential interaction between two ibuprofen enantiomers was studied after intravenous administration of R-(–)-, S-(+)- and racemic ibuprofen to rabbits. The total body clearance values calculated by compartmental model analysis (0.65+0.21 for R-(–)-ibuprofen and 0.63+0.34 for S-(+)-ibuprofen) after intravenous administration of the racemate of ibuprofen were significantly smaller than those of individual enantiomers (0.95+0.23 for R-(–)-ibuprofen and 1.03+0.23 for S-(+)-ibuprofen), indicating that the enantiomer–enantiomer interaction results in a mutual inhibition. The enantiomeric interaction in the pharmacokinetic behaviour of ibuprofen after racemic administration is considered to be a result of an alteration in the metabolic or excretion phase (or both) rather than stereoselective protein binding in the systemic distribution.