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.
Geisslinger
G
G
Department of Pharmacology and Toxicology, University of Erlangen, FRG.
Schuster
O
O
Stock
K P
KP
Loew
D
D
Bach
G L
GL
Brune
K
K
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D001682:Biological Availability; D001711:Biotransformation; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism
D007052:Ibuprofen