ABSTRACT
The pharmacokinetics of milrinone were studied in sequential ascending doses in New York Heart Association Class III and IV patients receiving oral and intravenous medication. The parameters determined after parenteral administration were estimated by fitting the plasma concentration data to an open two-compartment body model. After oral medication, regression-independent parameters were determined. After either oral or parenteral administration of milrinone, plasma levels were dose dependent and the drug had an apparent first-order terminal elimination half-life of approximately 2 hr. The apparent volume of distribution was approximately 400 to 500 ml/kg, and total body clearance was approximately 130 ml/kg/hr. These values obtained in patients receiving milrinone were compared with those obtained for milrinone in volunteers, as well as those noted with the other inotropic bipyridine, amrinone. Milrinone's elimination from the blood stream patients was slower that that in normal healthy subjects and faster than amrinone's elimination in patients with congestive heart failure. Milrinone's pharmacokinetic parameters in these patients were unchanged after approximately 30 days of continuous oral medication.
Subject(s)
Aminopyridines/metabolism , Heart Failure/drug therapy , Pyridones/metabolism , Administration, Oral , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Amrinone , Clinical Trials as Topic , Half-Life , Humans , Infusions, Parenteral , Kinetics , Male , Milrinone , Pyridones/administration & dosage , Pyridones/therapeutic use , Random Allocation , Time FactorsABSTRACT
Thirty-nine healthy men received milrinone either orally or intravenously in two separate double-blind, placebo-controlled studies. The mean bioavailability, based on the area under the plasma concentration versus time curves, was 0.92. The plasma data for those subjects in the intravenous study were described by an open two-compartment model with a mean (+/- SD) apparent first-order terminal elimination rate constant (beta) of 0.86 (+/- 0.23) h-1, which corresponds to a half-life of 0.8 h. In the intravenous study, the renal clearance and total body clearance were 21.1 and 25.9 L/h, respectively. The corresponding values in the oral study were 23.8 and 29.7 L/h. Between 79.9 and 84.5% of the total doses were recovered in the urine samples taken at 0-24 h.
