THE PHARMACOKINETICS OF THE ENANTIOMERS OF FLURBIPROFEN IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Plasma and synovial fluid concentrations of the enantiomers of flurbiprofen were measured in 15 rheumatoid patients receiving 100 mg racemic flurbiprofen twice daily. Pharmacokinetic parameters showed considerable variability within the group of patients, although differences in S(+)/R(-) plasma concentration ratios were small. The average values (+/-s.d.) of oral plasma clearance, volume of distribution and elimination half-life for R(-)-flurbiprofen were 0.075 (+/-0.066) 1 min-1, 12.47 (+/-5.79) 1 and 138 (+/-61) min, respectively. The average values (+/-s.d.) of oral plasma clearance, volume of distribution and elimination half-life for S(+)-flurbiprofen were 0.057 (+/-0.035) 1 min-1, 12.81 (+/-4.43) 1 and 155 (+/-49) min, respectively. S(+)/R(-) ratios (+/-s.d.) rose from 1.06 (+/-0.12) to 1.75 (+/-0.61) at the end of the 12 h interval in plasma and from 1.18 (+/-0.13) to 1.47 (+/-0.24) over the measured time course in synovial fluid. Increases in S(+)/R(-) ratios may be clinically important as they demonstrate accumulation of the pharmacologically active species.