Pharmacology and toxicology of nizatidine.

In well-established animal models, nizatidine is a potent, specific, and competitive orally active H2-receptor antagonist. In rat and dog models, species in which the absorption, plasma half-life and routes of metabolism are similar to that of humans, nizatidine was three- to four-fold more active than cimetidine and was of similar potency to ranitidine. On repeated daily dosing in dogs for two weeks, no tolerance was developed to the pharmacological action. Following oral dosing to dogs, nizatidine reduced gastric acid secretion for up to 8 h suggesting that this compound could be used in humans with a once or twice daily dosage regime. Apart from its H2-antagonist activity on the gastric mucosa, nizatidine produced few effects on the cardiovascular, respiratory, or central nervous system of animals. Nizatidine was rapidly and well-absorbed orally in mice, rats, and dogs, was widely distributed in tissues and the majority of the dose was excreted in the urine within 24 h. A similar absorption and excretion profile has been seen in humans. The plasma half-life in each of the animal species was between 1 and 2 h and no accumulation of nizatidine or its metabolites was seen in rats or dogs after daily oral administration for long periods. Similarities in the pharmacokinetic profile of nizatidine in the laboratory animals and humans supported the selection of the mouse, rat, and dog for acute and chronic toxicity studies. Nizatidine was well-tolerated in animals after both intravenous and oral administration and following single or repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS)