Pharmacokinetics and dynamics of famotidine in patients with renal failure.

Abstract

1. Famotidine, a new histamine H2‐receptor antagonist was administered intravenously (20 mg) to 22 patients with end stage renal disease during a dialysis free interval (n = 6) and during different blood purification processes including haemodialysis (HD; n = 4), intermittent haemofiltration (HF; n = 4), continuous haemofiltration (CHF; n = 4) and continuous ambulatory peritoneal dialysis (CAPD; n = 4). The plasma, the dialysate/filtrate and the urine concentrations of famotidine were analysed by h.p.l.c. 2. In addition, intra‐gastric pH was measured by a long‐term‐pH probe in seven patients with renal failure and in six patients with normal renal function (control group) following 20 mg famotidine. 3. A 7 to 10 fold prolongation of famotidine's elimination half‐life (27.2 +/‐ 8.5 h; mean +/‐ s.d.) was observed in patients with renal failure as compared with the half‐life (2.6‐3.6 h) in subjects with normal renal function. 4. Total body clearance (CL) and volume of distribution (V) were found to be 33.5 +/‐ 10.1 ml min‐1 and 1.3 +/‐ 0.7 l kg‐1, respectively in patients with end‐ stage renal failure. 5. Blood purification processes have shown considerable variation in clearing famotidine from the body: 16.4 +/‐ 8.9 and 6.0 +/‐ 2.9% of the administered dose in HD with polysulphone and cuprophan membranes respectively, 7.7 +/‐ 5.2% in HF with a polyacrylonitrile membrane (each for 5 h), 4.5 +/‐ 1.1% in CAPD and 16.2 +/‐ 4.9% in CHF with a polysulphone membrane within 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and Pharmacodynamics of H2-Receptor Antagonists in Patients with Renal Insufficiency

“…Depending on the degree of renal dysfunction the t1/, of famotidine was prolonged from 3 to 27h, with a simultaneous and parallel decrease in CL and CLR (Gladziwa et al 1988a;Hachisu et al 1988;Inotsume et al 1989;Lin et al 1988;Takabatake et al 1985). Thus, depending on the extent of renal impairment, dosage should be reduced by 50 to 75%.…”

“…In addition, no clear association between the individual pharmacokinetic and pharmacodynamic data was discernible (Gladziwa et al I 988a). This might be due to a higher acid secretion in patients with renal insufficiency (Gladziwa et al 1988a(Gladziwa et al , 1991Goldstein et al 1967;Milito et al 1983Milito et al , 1985Ritz et al 1971;Shepherd et al 1973;Venkateswaran et al 1972). Moreover, an abnormal gastric emptying time and an impaired drainage of gastric acid might play a role (Gladziwa et al 1991a).…”

“…Haemodialysis with polysulphone membranes seems to be most effective, as it removes 16.4% of the dose. However, supplementation during or after any form of blood purification procedure is not necessary (Gladziwa et al 1988a;Langtry et al 1989). Reducing the dosage to one-third of the normal dose of 40mg orally or 20mg intravenously is recommended in patients with severe renal failure who 327 are undergoing blood purification procedures (Gladziwa et al 1988a;Inotsume et al 1990).…”

“…Ebihara et (1977); 400-600 Larsson et al (1979Larsson et al ( , 1981Larsson et al ( . 1982 Famotidine Gladziwa et al (1988a); 15-20 Lin et al (1988) Hachisu et al (1988 60/week Takabatake et al (1986) 40 20 10 Hachisu et al (1992) 75 tiw Lameire et al (1988b) 75 q24h 40 q24h Takabatake et al (1986) 75 q8h 75 q24h 75 q48h a ml/min/1.48m 2 .…”

Renal Effects of Peptic Ulcer Therapy

“…Therefore, dose reduction is recommended for all 4 H2-antagonists based on creatinine clearance (table I). All H2-antagonists are minimally cleared by dialysis (both haemodialysis and peritoneal dialysis) and do not need to be supplemented after dialysis (Aronoff et al 1988;Garg et al 1985;Gladziwa et al 1988;Somogyi & Gugler 1983). However, with newer more permeable membranes and increased use of continuous arteriovenous haemofiltration in the intensive care unit setting, there is the potential for increased drug loss with dialysis, although there are few data to support this.…”