LACK OF PRESYSTEMIC INVERSION OF (R)-IBUPROFEN TO (S)-IBUPROFEN IN HUMANS

Presystemic inversion of (R)- to (S)-ibuprofen has been proposed but n ot directly examined in humans. We investigated the bioavailability of the enantiomers of ibuprofen in 10 healthy volunteers. Low-dose racem ic ibuprofen (400 mg) was administered orally and intravenously (60-mi nute infusion), in random order. There were no significant differences between oral and intravenous doses for the area under the curve value s, terminal rate constants, clearances, metabolite formation clearance s, and serum protein binding for (R)- and (S)-ibuprofen. The bioavaila bilities of (R)-ibuprofen and total ibuprofen were 0.92 +/- 0.11 and 0 .95 +/- 0.08, respectively. The fractional inversion of (R) -ibuprofen was determined by two methods (stable isotope method and from the ste reochemical composition of the urinary metabolites) that gave similar estimates of inversion for oral dosing (0.56 +/- 0.12 and 0.60 +/- 0.0 7, respectively) and intravenous dosing (0.56 +/- 0.09 and 0.60 +/- 0. 06, respectively). We conclude that the bioavailability of both enanti omers of ibuprofen is complete and find no evidence of significant pre systemic inversion.