Effect of ranitidine hydrochloride (150 mg twice daily) on the pharmacokinetics of increasing doses of ethanol (0. 15, 0.3, 0.6 g kg-1)

摘要

1 The interaction of ranitidine hydrochloride (150 mg twice daily for 15 doses) with single doses (0.15, 0.3 and 0.6 g kg -1 ) of ethanol was investigated in a placebo controlled study in 24 male subjects. Ethanol was given 1 h after a standard breakfast to maximise a drug ethanol effect if there is one. A balanced incomplete block design was used in that each subject received two of the three ethanol doses in the presence or absence of ranitidine. Blood samples ( n = 18) were taken for 8h after dosing and blood ethanol concentrations (BAC) were determined by head space analysis using a validated gas liquid chromatographic method. 2 At the lowest dose of ethanol studied the pharmacokinetic profile was largely first order but at the higher doses the usual zero order kinetics were seen. Using the technique of simultaneous fitting across all doses the Km , and Vmax , constants were similar and close to literature value of 100 mg 1 -1 and 200–300 mg h 1 -1 respectively. 3 Ranitidine, in common with other H 2 -receptor antagonists tested under the same experimental conditions, caused a small rise in BAC. However this was only evident at the smallest dose of ethanol studied and in common with many other publications, no effects were seen at the higher doses. The mean rise in blood ethanol following the 0.15 g kg -1 dose was 2.6 mg dl -1 (13.3 mg dl -1 for placebo and 15.9 mg dl -1 for ranitidine) and this change is of no clinical relevance.