We investigated the effect of 4 days pretreatment with cimetidine (1.2g 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 0.140l·kg–1 (control), 0.141l·kg–1 (cimetidine) and 0.146l·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.
Key words cimetidine - ranitidine - tolbutamide - hepatic microsomal enzymes