Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure

J Pharm Pharmacol. 1995 Aug;47(8):651-5. doi: 10.1111/j.2042-7158.1995.tb05853.x.

Abstract

This study was designed to test a proposed dose modification for intravenous milrinone in congestive heart failure patients (CHF, NYHA I-II) with either moderate or severe renal impairment. All the patients were administered an intravenous loading dose of drug at 50 micrograms kg-1 over 10 min. This was followed by an 18 h maintenance infusion of milrinone at 0.45 or 0.35 micrograms kg-1 min-1 for the moderate (chromium-EDTA clearance of 31-75 mL min-1, n = 10) and severe renally impaired subjects (chromium-EDTA of clearance 10-30 mL min-1, n = 11), respectively. Plasma and urine samples were collected for up to 34 h and analysed for parent drug by validated HPLC methods. The mean (+/- s.d.) steady-state plasma concentrations of milrinone were within the therapeutic range (100-300 ng mL-1) for both groups, with values of 239 +/- 71 ng mL-1 and 269 +/- 32 ng mL-1 for the moderate and severe patients, respectively. No statistical differences were observed between the steady-state values for the two groups. With the exception of two patients per group, individual steady-state levels were also within the therapeutic range. Those outside the nominal range showed steady-state levels, ranging between 308 and 353 ng mL-1, that were not associated with any serious adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Chromium / urine
  • Edetic Acid / metabolism
  • Female
  • Half-Life
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Milrinone
  • Pyridones / administration & dosage
  • Pyridones / pharmacokinetics*
  • Reference Standards
  • Renal Insufficiency / complications
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / metabolism
  • Severity of Illness Index
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacokinetics*

Substances

  • Cardiotonic Agents
  • Pyridones
  • Vasodilator Agents
  • Chromium
  • Edetic Acid
  • Milrinone