Pharmacokinetics of famotidine, a new H₂-receptor antagonist, in relation to renal function

Summary

The pharmacokinetics of a new, potent H₂-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CL_CR 90–60 ml/min/1.48 m²) but was increased to 4.72 h in moderate renal failure (CL_CR 60–30 ml/min/1.48 m²), and to 12.07 h in severe renal failure (CL_CR below 30 ml/min/1.48 m²). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CL_CR above 60 ml/min/1.48 m² the normal daily dose of famotidine can be employed, but in those with a CL_CR between 60 and 30 ml/min/1.48 m² the dose should be reduced by half, and in patients with a CL_CR below 30 ml/min/1.48 m² a reduction by three quarters of the normal dose is recommended.