PHARMACOKINETICS AND METABOLISM OF DILTIAZEM IN RATS FOLLOWING A SINGLE INTRAARTERIAL OR SINGLE ORAL DOSE

Diltiazem (DTZ) 20 mg/kg was given to male Sprague-Dawley rats either orally (p.o.) or intra-arterially (i.a.) over a 5 min period (n = 6 fo r each group). Plasma concentrations of DTZ and its major basic metabo lites were determined by high performance liquid chromatography assay (HPLC) as previously described over a 10 h period. The major metabolit es found in the rat plasma were M(2), followed by Mg-6, M(A), M(1), an d then M(4). The metabolite M(x) was measurable only in some of the pl asma samples, and M(B) was not detected in this species. The mean appa rent half-life (t(1/2)) of the measurable metabolites were longer than the parent DTZ. The metabolism profiles were qualitatively similar be tween the two routes of administration. Quantitatively, however, the p lasma concentrations of the metabolites were higher after the i.a. rou te. These results are in agreement with a previous study reported in r abbits, and suggest that deacetylation of DTZ and M(A) in the blood is extremely important in this species.