Pharmacokinetics and pharmacodynamics of roxatidine in patients with renal insufficiency

1. Roxatidine acetate, a new histamine H2-receptor antagonist, was administered in the evening (75 mg p.o.) to eight patients with renal insufficiency (CLCR 8-17 ml min-1) for 12 days and plasma drug concentrations were measured. 2. Ambulatory intragastric pH was monitored following the last dose and values were compared with those on day 1 when all patients received a placebo. 3. The terminal elimination half-life (mean +/- s.d.) of roxatidine was 10.8 +/- 2.4 h and its oral clearance was 178 +/- 43 ml min-1. 4. During roxatidine treatment gastrin levels increased slightly (median 189 vs 289 ng l-1) and the hyperparathyroid status of the patients was almost normalized (parathyroid hormone levels: median 199 vs 132 ng l-1). 5. The mean latency to a gastric pH of at least 4 was 4.3 +/- 1.4 h. The duration of action (intragastric pH > 4) was 10.6 +/- 3.9 h. 6. As in a pilot study with six patients (CLCR < or = 17 ml min-1) the recommended dosage regimen (75 mg 48 h-1) was unable to maintain gastric pH > 4 for more than 6 h, daily nocturnal intake of 75 mg roxatidine acetate appears appropriate to elevate gastric pH > 4 for a sufficient period of time.