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

Abstract

I Plasma levels of benoxaprofen were measured in eight subjects 2-168 h after a single oral dose of 100 mg. Pharmacokinetic parameters were estimated by the NON-LIN computer programme using the two-compartment open model. Mean half-lives of absorption, distribution and elimination were respectively 0.4, 4.8 and 37.6 hours. Volumes of distribution were 6.8 and 3.2 litres for the central and peripheral compartments respectively. 2 Eleven subjects in groups of three or four were given 25 mg/day, 50 mg/day or 100 mg two times daily for 11 days. Their plasma levels were compared with those predicted from the above parameters, which were adjusted for individual body weights and elimination half-lives. Steady-state plasma levels were predicted in each case, and a reasonable degree of accuracy (mean 91 %) achieved. 3 There was no tendency for observed and predicted levels to diverge as the dose was increased, and there was no evidence of any change in the disposition of benoxaprofen on repeated dosing. 4 The pharmacokinetic parameters were used to predict steady state plasma levels for various dosage regimens.

Preliminary studies of absorption and excretion of benoxaprofen in man.

“…After reaching a peak, the mean plasma concentrations fell slowly. The mean plasma half-life was found to be long, in most subjects between 30-35 h, although a considerably longer half-life was recorded in some individuals (Chatfield, Tarrant, Smith & Speirs, 1977). The related areas under the 0-72 h mean plasma level curves were 397, 940 and 1480 jig h ml-', indicating a reasonably linear dose-response in absorption over this dosage range.…”

“…The levels of benoxaprofen in plasma and urine samples were assayed by gas chromatography using flame ionization for detection of the methyl ester derivative. The method will be described in detail elsewhere (Chatfield & Woodage, 1977), and has a sensitivity down to 0.1 jIg/ml.…”

Pharmacology, Clinical Efficacy, and Adverse Effects of the Nonsteroidal Anti‐Inflammatory Agent Benoxaprofen

“…'~, '~ Taking food with benoxaprofen delays absorption and reduces peak serum levels but does not significantly alter the total amount of the dose absorbed.lg Steady state serum levels of benoxaprofen are achieved in 6-8 days but may vary greatly. 19,20 In common with most of the other NSAIDs, the apparent volume of distribution of benoxaprofen is small (1 4 rnl/kg).,O Benoxaprofen is approximately 99% protein bound in the serum in the doses employed ~I i n i c a l l y .~~~ 23a After rectal administration, benoxaprofen is absorbed and plasma levels reach 80% of those attained after oral administration of a similar dose.,, Overall absorption reaches approximately 80% of that achieved with oral administration.…”