Pharmacokinetics and biotransformation of methane sulphonanilides with anti-inflammatory activity in the rat and monkey--comparison with piroxicam.
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. Both sulphonamides were rapidly oxidized at positions 1 and 3. The pharmacokinetics of DF-PMS and of piroxicam were examined in the rat and monkey (Macaca fascicularis). 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. 1-Oxo DF-PMS exhibited shorter half-lives, larger volumes of distribution and higher total clearance rates than piroxicam in the animal model studied.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D007189:Indans / Q000378:metabolism*; D007192:Indenes / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis; D010894:Piroxicam; D051381:Rats; D011919:Rats, Inbred Strains; D013843:Thiazines / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D007189:Indans; D007192:Indenes; D013843:Thiazines; D010894:Piroxicam; C039392:N-(6-phenoxyindan-5-yl)methanesulfonamide; C039393:N-(6-(2,4-difluorophenoxy)indan-5-yl)methanesulfonamide