Nizatidine disposition in subjects with normal and impaired renal function

Abstract

To test the hypothesis that renal insufficiency alters nizatidine disposition, we determined the pharmacokinetics of nizatidine and its major metabolite after a single oral dose in normal volunteers and patients with various degrees of renal dysfunction, after a single intravenous dose in normal volunteers and patients with severe renal failure and during hemodialysis. After intravenous administration the elimination half-life increased from 1.5 +/- 0.2 hours in normal volunteers to 6.9 +/- 3.3 hours in patients with renal failure. The plasma clearance decreased from 0.59 +/- 0.07 L/kg/hr in normal volunteers to 0.14 +/- 0.02 L/kg/hr in patients with renal failure. Nizatidine bioavailability was nearly 100% in normal volunteers but decreased to 75% in patients with renal failure. The volume of distribution was 1.3 +/- 0.1 L/kg in normal volunteers and was not different in patients with renal failure. Nizatidine protein binding was about 30% in normal and uremic plasma. The drug was not substantially removed by hemodialysis. Patients with creatinine clearances less than 50 ml/min/1.73 m2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m2 should receive 150 mg nizatidine every other night.

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

“…Pharmacokinet. 24 (4) 1993 in patients with anuria than in healthy volunteers (Aronoff et al 1988;Callaghan et al 1987a). Therefore, patients with CLcR <50 ml/min should receive 150mg of nizatidine once each evening and those with CLcR <20 ml/min should receive nizatidine 150mg every second night.…”

“…In patients with anuria, the F of orally administered nizatidine was decreased to 75% (Aronoff et al 1988). Nizatidine protein binding was 30% both in normal and uraemic plasma.…”

“…To avoid accumulation of the drug, the dosage of nizatidine in patients with renal insufficiency should be adjusted accordingly (Aronoff et al 1988): where CLCR is 50 to 20 mlfmin/1.73m2, the total daily dose is 150mg; where CLCR is < 20 mlfmin/ 1.73m2, 150mg should be given on alternate days.…”

“…Less than 25% of the nizatidine dose was recovered in unchanged form in the urine of patients with moderately severe renal dysfunction. The apparent nonrenal clearance (CLNR) and Vd did not change with renal function (Aronoff et al 1988).…”

Oral Bioavailability of Nizatidine and Ranitidine Concurrently Administered with Antacid

“…Dosage reduction, however, is recommended in renal insufficiency. 10 Plasma concentrations of nizatidine in the present study were not greatly impaired by concurrent administration of antacid. There was a moderate shift toward the right in the plasma concentration -time curve.…”