PHARMACOKINETICS AND EFFECTS ON BLOOD-PRESSURE OF A SINGLE ORAL DOSE OF MILRINONE IN HEALTHY-SUBJECTS AND IN PATIENTS WITH RENAL IMPAIRMENT

Milrinone, a new, nonglycosidic inotropic agent with peripheral vasodilating properties, was given as a single oral 5 mg dose to 7 healthy subjects, 7 patients with moderate renal impairment (CRI I, creatinine clearance 30-63 ml/min) and 7 patients with severe renal impairment (CRI II, creatinine clearance 9-29 ml/min). All except one of the patients with renal impairment had hypertension. The mean urinary recovery of milrinone was 82% in healthy subjects, the renal clearance was 288 ml/min and the plasma half-life (t12) was 0.94 h. In CRI the mean plasma t1/2 was prolonged (CRI I 1.78 h, CRI II 3.24 h). There was a significant linear relationship between creatinine clearance and the elimination rate constant, and between creatinine clearance and the renal clearance of milrinone. During the study day there was a tendency to a decrease in supine BP from 1 to 6-8 h after dosing, with the maximal decrease at 2-3 h (healthy subjects 118/71 .fwdarw. 107/56, CRI 159/95 .fwdarw. 136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2-6h after dosing. Changes in BP and HR are difficult to evaluate since the study was not placebo-controlled. The plasma elimination rate of milrinone was decreased in CRI and dose adjustment may be necessary. Placebo-controlled studies of milrinone in hypertensive patients would be required to validate its possible antihypertensive effect.