Inhibition of pentoxifylline clearance by cimetidine.
The effect of cimetidine on the single-dose pharmacokinetics of pentoxifylline and one of its major metabolites, 3,7-dimethyl-1-(5-hydroxyhexyl)xanthine (1), was examined in two groups of male Sprague-Dawley rats (6 rats/group) after the administration of pentoxifylline (1 mg/kg) alone and following a 50 mg/kg iv dose of cimetidine. The addition of cimetidine resulted in a 37% decrease in pentoxifylline clearance (23.8 +/- 7.5 versus 15.0 +/- 3.2 mL/min; p less than 0.03). No changes in the volume of distribution of pentoxifylline or in the total area under the plasma concentration-time curve for 1 were observed with the addition of cimetidine. The mechanism of this metabolic interaction is probably cimetidine-induced inhibition of hepatic microsomal enzymes, which blocks the major excretory pathways for pentoxifylline. Further studies are warranted in humans to determine the existence and clinical significance of this interaction.
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D003864:Depression, Chemical; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010431:Pentoxifylline / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013805:Theobromine / Q000031:analogs & derivatives*
D002927:Cimetidine; C025189:lisofylline; D013805:Theobromine; D010431:Pentoxifylline