The relationship between the pharmacokinetics of amrinone in the marmoset and platelet effects

The pharmacokinetic characteristics of amrinone have been studied in six female marmosets following oral administration of 1, 12.5, 25, 50 and 75 mg.kg-1 and an intravenous dose of 1mg.kg-1. The mean plasma AUC0 infinity was determined at each dose level; the values obtained were 2.5, 18.7, 33.9, 103 and 312 micrograms.h.ml-1 for the oral doses of 1, 12.5, 25, 50 and 75 mg.kg-1 respectively and 1.9 micrograms.h.ml-1 for the intravenous dose of 1mg.kg-1. Mean maximum observed plasma concentrations were 0.6, 7.1, 11.7, 23.7 and 40.0 micrograms.ml-1 respectively following oral doses. Over the range 1 to 50 mg.kg-1 the AUC0 infinity was linear; at 75 mg.kg-1 the AUC0 infinity was disproportionately greater. Elimination appeared to be first order over the dose range 1 to 50 mg.kg-1 and the t1/2 in the marmoset was approximately 1 to 3 hours over this dose range. The plasma levels achieved are discussed in relation to the observed effects on the platelet population in this species following chronic administration at high dose levels.