Lidocaine disposition—Sex differences and effects of cimetidine

Publisher Website
Google Scholar
Abstract
The effects of pretreatment with cimetidine [a histamine H2-antagonist] (1 g daily for 3 days) on the disposition of lidocaine were examined in 18 healthy subjects, 7 of whom were chronic cigarette smokers. Each subject received separate oral (200 mg) and i.v. (75 or 100 mg) doses of lidocaine before and after cimetidine. After cimetidine, lidocaine apparent oral clearance (Clo) reduced 42 .+-. 7%; oral bioavailability increased 35 .+-. 10%; and systemic clearance (Cls) and volume of distribution at steady-state (Vdss) decreased 21 .+-. 6% and 20 .+-. 7%. Elimination t1/2 [half life] was unchanged. Calculated values for Cls after cimetidine based on reduction in Clo and consequent decrease in hepatic extraction ratio correlated significantly with observed values for Cls (r = 0.67). Women had larger Vdss (64 .+-. 19%), longer t1/2 (50 .+-. 18%) and greater oral lidocaine bioavailability (63 .+-. 29%) than did men. There was no sex difference in and no influence of cigarette smoking on the effect of cimetidine. Cimetidine evidently reduces metabolic clearance of lidocaine. The consequent reduced hepatic extraction explains the observed reduction in Cls.