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 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 (t1/2) 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----107/56, CRI 159/95----136/79 mmHg). The same degree of change was seen in standing BP. A slight rise in standing HR was seen from 2-6 h 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.
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D003404:Creatinine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D020105:Milrinone; D011187:Posture; D011728:Pyridones / Q000097:blood / Q000494:pharmacology* / Q000652:urine
D002316:Cardiotonic Agents; D011728:Pyridones; D003404:Creatinine; D020105:Milrinone