Nizatidine, an H2-blocker. Its metabolism and disposition in man

Abstract

The disposition of a single oral dose of about 150 mg of nizatidine, an H2-blocker, was studied in five men. Plasma levels of both parent drug and radioactivity peaked in 1-3 hr. Nizatidine accounted for about 60% of the plasma radioactivity. The t1/2 of nizatidine was 1.6 hr. About 35% of nizatidine became bound to plasma proteins in vitro, particularly to alpha-1-glycoprotein. Warfarin, acetaminophen, phenobarbital, propantheline, diazepam, and propranolol did not notably affect the amount of nizatidine bound. Two to 3 times more radioactivity was in plasma than in blood cells or saliva. Greater than 90% of the dose of nizatidine was excreted in urine, probably by glomerular filtration and active tubular secretion. Nizatidine accounted for about 65% of the urinary radioactivity. The major metabolite of nizatidine was N2-monodesmethylnizatidine; it represented about 7% of the nizatidine dosage. Another metabolite, constituting about 5% of the dose, is proposed to be nizatidine N2-oxide. Nizatidine sulfoxide also may be a minor metabolite of nizatidine.