Nizatidine disposition in subjects with normal and impaired renal function

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 m 2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m 2 should receive 150 mg nizatidine every other night. Clinical Pharmacology and Therapeutics (1988) 43 , 688–695; doi: 10.1038/clpt.1988.97