title: Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure.
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)
authors.affiliation: Sanofi Winthrop, Sanofi Research Division, Alnwick, Northumberland, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Woolfrey
authors.forename: J
authors.initials: J
authors.lastname: Hegbrant
authors.forename: H
authors.initials: H
authors.lastname: Thysell
authors.forename: P A
authors.initials: PA
authors.lastname: Fox
authors.forename: D W
authors.initials: DW
authors.lastname: Lendrem
authors.forename: G F
authors.initials: GF
authors.lastname: Lockwood
authors.forename: K
authors.initials: K
authors.lastname: Lasher
authors.forename: J
authors.initials: J
authors.lastname: Rogers
authors.forename: D
authors.initials: D
authors.lastname: Greenslade
mesh_terms: D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002857:Chromium / Q000652:urine; D004492:Edetic Acid / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020105:Milrinone; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012015:Reference Standards; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D012720:Severity of Illness Index; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D002316:Cardiotonic Agents; D011728:Pyridones; D014665:Vasodilator Agents; D002857:Chromium; D004492:Edetic Acid; D020105:Milrinone