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

Abstract

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 1.141/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, CLCR 90-60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60-30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR 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 CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.

Pharmacokinetics and dynamics of famotidine in patients with renal failure.

“…The volume of distribution in dialysis free patients and patients undergoing CHF did not differ significantly from that in subjects with normal kidney function. These findings are in agreement with those of Takabatake et al (1986).…”

“…The study of Takabatake et al (1985) on the disposition of famotidine in patients with renal failure revealed that with decreasing creatinine clearance the half-life of famotidine was significantly prolonged. This is supported by our finding in patients with a creatinine clearance less than 5 ml min-1.…”

“…Many investigations have documented that the increased incidence of peptic ulcer and gastrointestinal bleeding in patients with renal insufficiency is partly due to the hypersecretion of gastrin and hydrochloric acid (Goldstein et al, 1967;Ritz et al, 1971;Venkateswaran et al, 1972;Shepherd et al, 1973;Milito et al, 1983Milito et al, , 1985.…”

“…Following i.v. administration in normal subjects about 72% of a dose is excreted unchanged with a renal clearance of about 222 to 304 ml min-', exceeding the glomerular filtration rate (Takabatake et al, 1985;Kroemer & Klotz, 1987). This suggests that tubular secretion plays a predominant role in the renal elimination of famotidine.…”

“…The plasma half-life and steady state volume of distribution in normal subjects have been reported to be 2.6 to 3.6 h and 1.13 to 1.14 1 kg-l, respectively. The half-life is prolonged in patients with kidney failure and total body clearance (CL) depends on renal function (Takabatake et al, 1985;Kroemer & Klotz, 1987).…”