Lack of efficacy of cimetidine and ranitidine as inhibitors of tolbutamide metabolism.
We investigated the effect of 4 days pretreatment with cimetidine (1.2 g daily) and ranitidine (0.3 g daily) on tolbutamide disposition in an open randomised, cross-over study design involving 8 healthy adult male volunteers. Control half-life of tolbutamide 6.29 h was not significantly altered by cimetidine (6.93 h) or ranitidine (6.97 h). The corresponding apparent oral clearance (ml.min-1.kg-1) were not significantly different: 0.26 (control), 0.24 (cimetidine) and 0.25 (ranitidine). Apparent volume of distribution was also unaltered 0.140 l.kg-1 (control), 0.141 l.kg-1 (cimetidine) and 0.146 l.kg-1 (ranitidine). It is suggested that the hepatic monooxygenase isozyme that catalyses the rate-limiting conversion of tolbutamide to its hydroxy derivative is not susceptible to the inhibitory effect of cimetidine or ranitidine.
Adebayo
G I
GI
Department of Pharmacology, College of Medicine, Lagos, Nigeria.
Coker
H A
HA
D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D011899:Ranitidine / Q000494:pharmacology*; D014044:Tolbutamide / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*
D002927:Cimetidine; D011899:Ranitidine; D014044:Tolbutamide