Pharmacokinetics of nizatidine in dogs and rats

1. Plasma levels of nizatidine and two metabolites (N-desmethyl nizatidine and nizatidine S-oxide) were studied in dogs and rats.

2. The time-courses of plasma concentration of nizatidine after i.v. and oral administration to dogs well fitted a two-compartment model. Absorption after oral administration was rapid, and the peak plasma level (C_max) and area under the plasma concentration-time curve (AUC) were proportional to doses. Absolute bioavailability was close to 100%, indicating that nizatidine has a negligible first-pass effect.

3. Nizatidine was eliminated by apparent first-order kinetics after i.v. administration to rats, and the elimination in rats was faster than in dogs. Bioavailability in rats was 72.4%, indicating a slight first-pass effect in rats.

4. When plasma clearance (Cl_p), or volume of distribution (V_d.β), of nizatidine were plotted against animal body weight on a log-log scale, good correlations were obtained for rats, dogs and humans.

5. Peak levels (C_max) of two metabolites were reached at 0.5–1.0?h after oral and i.v. administration of nizatidine to dogs. The elimination curves of the two metabolites were similar to that of nizatidine. Significant relationships were found between doses of nizatidine and C_max or AUC of both metabolites.