The effect of single doses of cimetidine on estimated hepatic blood flow.

Controversy exists as to whether H2-receptor antagonists decrease hepatic blood flow. This study examined the effect of single doses of cimetidine 300 and 600 mg po on apparent hepatic blood flow as estimated by indocyanine green (ICG) clearance. A double-blind, repeated-measure study was performed in nine supine healthy men. Following an overnight fast, placebo or cimetidine was administered one hour prior to ICG 0.5 mg/kg iv. Plasma samples were obtained serially for a period of 20 minutes following dye administration and stored at -70 degrees until high performance liquid chromatographic analysis. Cimetidine had no apparent effect on mean +/- SD ICG clearance following placebo, cimetidine 300 mg, and cimetidine 600 mg (366 +/- 66 vs. 336 +/- 55 vs. 350 +/- 58 ml/min/m2, respectively; NS). Corresponding values for estimated hepatic blood flow were 632 +/- 109, 580 +/- 103, and 617 +/- 112 ml/min, respectively; NS. No statistically significant changes in ICG half-life or volume of distribution at steady state occurred as a function of treatment. Contrary to previous reports, single-dose cimetidine administration appeared to have no appreciable effect on hepatic blood flow. These results implicate cimetidine binding to the cytochrome P-450 system as the sole mechanism responsible for inhibition of the systemic clearance of co-administered drugs metabolized by the liver.