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J Pharm Pharmacol ; 47(8): 651-5, 1995 Aug.
Article in English | MEDLINE | ID: mdl-8583366

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)


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