STEREOSELECTIVE DISPOSITION OF FLURBIPROFEN IN UREMIC PATIENTS

1 Both single and multiple oral doses of 50 mg racemic flurbiprofen were given to eight patients with mild to moderate renal impairment. The plasma and urine concentrations of the R- and S-enantiomers of flurbiprofen and its major metabolites were measured by a stereoselective h.p.l.c. assay. 2 For R-flurbiprofen the oral clearance (mean +/- s.d.: 38.3 +/- 12.8 vs 30.8 +/- 11.5 ml min-1) and volume of distribution (V(z); 17.6 +/- 3.9 vs 14.6 +/- 2.5 l) were significantly greater (P < 0.05) than for the S-enantiomer. A significantly greater (P < 0.05) percent of the dose was excreted in the urine in the R-configuration (16.4 +/- 6.0 vs 10.9 +/- 4.2%). 3 Plasma protein binding of the enantiomers of flurbiprofen was determined by ultrafiltration. The unbound clearance and unbound V(z) were not different between enantiomers consistent with the (not significantly) greater percent unbound of R-flurbiprofen (0.079 +/- 0.014%) vs S-flurbiprofen (0.064 +/- 0.015%). 4 Relative to normal volunteers, the uraemic subjects exhibited a significantly greater (P < 0.05) oral clearance, V(z) and percent unbound for both enantiomers; unbound clearance and unbound V(z) did not differ from healthy controls. 5 The disposition of flurbiprofen enantiomers was not changed upon multiple dosing and no evidence of futile cycling was found. Adjustment of flurbiprofen dosing rate in uraemic subjects is not indicated on the basis of pharmacokinetics.