Pharmacokinetics and dynamics of famotidine in patients with renal failure

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)