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  • Title: Lack of efficacy of cimetidine and ranitidine as inhibitors of tolbutamide metabolism.
    Author: Adebayo GI, Coker HA.
    Journal: Eur J Clin Pharmacol; 1988; 34(6):653-6. PubMed ID: 3169118.
    Abstract:
    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.
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