Pharmacokinetics and biotransformation of methane sulphonanilides with anti-inflammatory activity in the rat and monkey—comparison with piroxicam

Abstract

1. The biotransformation of N-(6-phenoxyindan-5-yl)methansulphonamide (PMS) and of its 2′,4′-difluoro derivative (DF-PMS) were studied in vitro using rat-liver homogenate followed by h.p.l.c. separation and mass-spectrometric identification of metabolites.

2. Both sulphonamides were rapidly oxidized at positions 1 and 3.

3. The pharmacokinetics of DF-PMS and of piroxicam were examined in the rat and monkey (Macaca fascicularis).

4. Considerable concentrations were achieved in the plasma only by the 1-oxo metabolite of DF-PMS but not by the unchanged drug, indicating that the administered compound was a pro-drug of the active principle.

5. 1-Oxo DF-PMS exhibited shorter half-lives, larger volumes of distribution and higher total clearance rates than piroxicam in the animal model studied.