The effects of gender and oral contraceptive steroids on the pharmacokinetics of (R)-ibuprofen were studied in groups of healthy adult males, females and oral contraceptive steroid (OCS) using females. The values of AUC, CLpo, t1/2 and Vss, app did not differ significantly between the groups. Similarly, the percentage unbound of (R)-ibuprofen in pooled plasma from the three groups was not statistically different. Since chiral inversion is the major determinant of (R)-ibuprofen clearance in humans, it may be inferred from these data that gender and OCS have little or no effect on conversion of (R)-ibuprofen to the pharmacologically active S-enantiomer. Moreover, it is unlikely that hormonal factors influence the activity of the human hepatic long-chain fatty-acid:CoA ligase, the enzyme mediating the rate limiting step of (R)-ibuprofen inversion.
PIP: In Australia, clinical researchers studied the effects of gender and oral contraceptive (OC) steroids on the pharmacokinetics of (R)-ibuprofen in 8 healthy adult males (mean age = 21 years), adult females (24 years), and OC users (22 years). There were no statistically significant differences between males, females, and OC users for any pharmacokinetic parameter for (R)-ibuprofen. These parameters included areas under the plasma total concentration-time curve (AUC), maximal plasma concentration, time to maximal plasma concentration, half-life, CLpo, and apparent steady-state volumes of distribution. The AUC to the last data point observed for (S)-ibuprofen (derived from (R)-ibuprofen) was similar, suggesting that hormonal factors do not affect plasma clearance of (S)-ibuprofen. The average percentages unbound of (R)- and (S)-ibuprofen across the concentration was not statistically different between the groups: 1.82% and 2.84% for males, 1.83% and 3.01% for females, and 2.1% and 2.97% for OC users, respectively. The mean fraction unbound of (S)-ibuprofen was 53.6% greater than that of (R)-ibuprofen. Since chiral inversion may explain 62-92% of (R)-ibuprofen clearance in humans, these data may suggest that gender and OCs do not effect or have only a limited effect on the conversion of (R)-ibuprofen to the pharmacologically active S-enantiomer. These findings indicate that hormonal factors probably do not affect the activity of the human hepatic long-chain fatty-acid:CoA ligase, the enzyme mediating the rate limiting step of (R)-ibuprofen inversion.