Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis

Abstract

Ranitidine kinetics in renal failure were evaluated in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD). On separate occasions each patient received either 50 mg intravenously (i.v.) or 150 mg orally of ranitidine HCl. Following i.v. administration, the plasma concentration vs time curve was best described by a two compartment model with firstorder elimination. The mean +/- SD distribution and elimination rate constants were 2.47 +/- 0.78 and 0.098 +/- 0.013 h, respectively. The area under the serum concentration vs time curve after the i.v. dose was 5979 +/- 2870 micrograms X h X l-1, resulting in a mean volume of distribution of 76.8 l and a total body clearance of 126 ml X min-1. Following oral administration the observed maximum plasma concentration was 904 +/- 483 micrograms X l-1 at 4.2 +/- 1.8 h, and the bioavailability was 69.7 +/- 35.6%. The peritoneal clearance of ranitidine was 3.2 +/- 0.7 and 2.6 +/- 0.6 ml X min-1 for the i.v. and oral groups, respectively. The amount of drug removed by dialysis was 561.2 +/- 336.2 micrograms for the i.v. and 1197.1 +/- 602.3 micrograms for the oral group. Four patients in the i.v. group had urine output during the study period with renal ranitidine clearance values of 9.9 +/- 9.9 ml X min-1. Two patients in the oral group had urine output and corresponding renal ranitidine clearance values of 5.1 and 20.1 ml X min-1. A dosage regimen for ranitidine is proposed based on ranitidine kinetics in patients undergoing CAPD.

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

“…F (54.3 ± 13.5%) is comparable with that found in normal individuals (52%) [Comstock et al 1989;Garg et al 1983;Sica et al 1987). Cmax is delayed in patients with renal impairment compared with that in individuals with normal renal function (3 to 4h vs 2h) [McGonigle et al 1982a;Sica et al 1985b].…”

“…During a single haemodialysis session of 4 to 6h the serum ranitidine concentrations decreased by 60% after intravenous administration and by 55% after oral administration (Comstock et al 1989;McGonigle et al 1982a,b). The quantity of drug removed represented less than 10% of the administered dose (Comstock et al 1988(Comstock et al , 1989Garg et al 1985;Sica et al 1985a). During haemofiltration, Gladziwa et al (1988b) found that 17.1 ± 6.3% of the administered dose was removed, whereas Pollock et al (1986) found only a 2.1 ± 1.4% removal.…”

“…However, neither investigator advocated any drug supplementation after haemofiltration. The dialytic removal of ranitidine during continuous ambulatory peritoneal dialysis (CAPO) was low «2% of the administered dose) [Cavagna et al 1987;Sica et al 1985aSica et al , 1987. These data suggest that additional ranitidine administration is not required after any mode of dialysis therapy.…”

Pharmacokinetics and dynamics of famotidine in patients with renal failure.

“…Based on the extent of extra- corporeal clearance cimetidine has been categorised as a slightly dialysable (5 to 20%) drug (Knoben & Anderson, 1983). A recent report on the peritoneal clearance of ranitidine revealed that only 1.3 and 0.9% of the administered dose was removed by CAPD over a period of 20 h following intravenous and oral routes, respectively (Sica et al, 1987).…”

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

“…Conversely, Sica et al [20] analyzed the pharmacokinetics of H2B using ranitidine and reported that H2B clearance was decreased in continuous ambulatory PD patients compared to that observed in individuals with normal kidney function. Therefore, acid suppression with H2B treatment may be more powerful than that obtained with PPIs in PD patients.…”