Pharmacokinetics and bioavailability of diltiazem (CRD-401) in dog.

Pharmacokinetic behaviour of a new coronary vasodilator, the d-cis-isomer of 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride (diltiazem, CRD-401), as well as the bioavailability study of the release controlled tablet Herbesser have been described by using the proposed specific assay method of unchanged diltiazem in plasma. Quantitive analysis after its oral administration evidenced that diltiazem was absorbed through the gastrointestinal tract in the intact form. In the kinetical experiment, where diltiazem was administered i.v., a rapid and large distribution of diltiazem into tissue compartment were suggested. In the bioavailability study, a comparison of plasma concentrations of diltiazem between the two different crystals and the micronized powder resulted in no difference in their bioavailability, when they were administered in the form of capsules. In the single and multiple administration of the release controlled tablet, a slow and continuous absorption of diltiazem was observed. Elimination rate after the multiple dose regimen was in good agreement with that in a single dose, thereby indicating no accumulation in the body.