Pharmacokinetics of moricizine HCl.

Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.