Pharmacokinetics of S(+)- and R(-)-ibuprofen in volunteers and first clinical experience of S(+)-ibuprofen in rheumatoid arthritis

S(+)‐,R(‐)‐ or racemic ibuprofen was administered orally to volunteers in doses of 150 mg, 300 mg and 500 mg pure S(+)‐, 300 mg pure R(‐)‐ and 600 mg racemic ibuprofen. The pharmacokinetic parameters in humans showed that S(+)‐ibuprofen was not inverted to R(‐)‐ibuprofen, whereas R(‐)‐ibuprofen was inverted to S(+)‐ibuprofen to a variable degree. S(+)‐ibuprofen and R(‐)‐ibuprofen given alone more rapidly reached significantly higher maximal plasma concentrations than after the same doses of the racemic compound. The elimination half‐lives and clearance values for all three forms of ibuprofen were comparable. The mean residence time of S(+)‐ibuprofen after R(‐)‐ and racemic ibuprofen was significantly longer than after administration of the pure S(+)‐enantiomer. Judged by the AUC, the bioavailability of S(+)‐ibuprofen was independent of the dose within the range tested. Administration of S(+)‐ibuprofen to 6 rheumatic patients showed that the pharmacokinetic behaviour of S(+)‐ibuprofen in patients was similar to that found in volunteers. S(+)‐ibuprofen proved to be an effective analgesic antirheumatic drug in the dose range 1 to 1.5 g/day.