Preliminary studies of absorption and excretion of benoxaprofen in man.

Abstract

1 Benoxaprofen is a new acidic anti‐inflammatory compound which was well absorbed after oral administration to man. 2 Single doses of 100, 200 and 400 mg produced mean peak concentrations in the plasma of 13.0, 33.5 and 45.3 microgram respectively, and the plasma half‐life of the compound was between 30 and 35 hours. 3 Multiple dosing with 25 and 50 mg every 24 h achieved an equilibrium conentration in the plasma after 6‐8 days, while dosing with 100 mg every 12 h enabled equilibrium to be reached in 3‐6 days. Plasma concentrations between 35 and 45 microgram/ml were achieved by giving 100 mg doses every 12 hours. 4 Absorption of benoxaprofen was delayed when the drug was given with food, but the total amount absorbed remained the same. 5 The effect of milling the material to small particle size (19 micron) was to increase the rate of absorption compared to that of unmilled material (58 micron). 6 Benoxaprofen was well tolerated by healthy male subject in the doses given.

Stereospecific inversion of (R)-(−)-benoxaprofen in rat and man

“…The inversion half-life in man is much longer than in rat and also considerably longer than the elimination half-life of ca. 30 h (13). Humans are unlikely to build up a preponderance of the (S)-( + )-enantiomer.…”

Fatal Self-poisoning with Benoxaprofen

“…The serum benoxaprofen concentration in this patient 40 h after admission was 811 mg/1, some 20 times greater than that usual with normal dosage (Smith et al, 1977). Blood and urine screens for paracetamol, barbiturate and salicylate were negative.…”

Pharmacokinetic studies with benoxaprofen in man: prediction of steady‐ state levels from single‐dose data.

“…The plasma levels of benoxaprofen used for this work were determined during the single and multiple dose studies carried out in normal subjects by Smith et al (1977). At least 2 weeks before the multiple dose studies, terminal plasma half-lives had been determined by giving a single oral dose of 50-200 mg to each subject (except to one in the 25 mg/day group who was therefore excluded from this analysis).…”

“…(a) ka, the absorption rate constant, was halved to 0.86 h-1 to allow for the slower absorption observed in non-fasted subjects (Smith et al, 1977).…”

“…This is particularly important for a drug such as the novel anti-inflammatory compound benoxaprofen, with a plasma half-life in man exceeding 24 h (Smith, Goulbourn, Burt & Chatfield, 1977). This drug will accumulate on repeated dosing until a steady-state level is achieved after several days.…”