Pharmacokinetic profile of benoxaprofen in subjects with normal and impaired renal function, prediction of multiple-dose kinetics.
The pharmacokinetic profile of benoxaprofen given as a single oral dose of 600 mg was determined comparatively in 5 healthy volunteers and in 15 patients with various degrees of renal insufficiency (5 of whom were undergoing maintenance hemodialysis). In normal subjects, the half-absorption period (Ka) was 0.63 hours. A mean maximum concentration of 47.3 micrograms/ml could be predicted at 3.6 hours after the dose intake. Serum level decrease was particularly slow. The overall elimination rate constant, Ke, was 0.0234(h-1) and biologic half-life amounted to 28.8 hours. Values for total clearance (Ct=4.8 ml/min/1.73 m2) and renal clearance (Cr=1.6 ml/min/1.73 m2) were low. Of the administered dose of benoxaprofen, 13.9% was recovered in the urine over a 24-hour period. Renal insufficiency did not induce major changes in pharmacokinetic parameters. Under such conditions, it seems advisable to reduce the dose to one-half only in patients with a creatinine clearance of less than 10-20 ml/min/1.73 m2. Predicted serum levels theoretically achieved after repeated administration of a 600-mg dose of benoxaprofen every 6, 12, 24, 36 and 48 hours were calculated. From this evaluation, it appears that therapeutically effective and adequate levels could be obtained after administration of a 600-mg dose every 12 ot 24 hours.
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011422:Propionates / Q000008:administration & dosage / Q000378:metabolism*; D006435:Renal Dialysis; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D011422:Propionates; C011677:benoxaprofen