Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock.
| Title: | Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock. |
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| Authors: | Lindsay CA; Division of Pediatric Critical Care, University of Texas Southwestern Medical Center and Children's Medical Center of Dallas, 75235-9063, USA.; Barton P; Lawless S; Kitchen L; Zorka A; Garcia J; Kouatli A; Giroir B |
| Source: | The Journal of pediatrics [J Pediatr] 1998 Feb; Vol. 132 (2), pp. 329-34. |
| Publication Type: | Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Mosby Country of Publication: United States NLM ID: 0375410 Publication Model: Print Cited Medium: Print ISSN: 0022-3476 (Print) Linking ISSN: 00223476 NLM ISO Abbreviation: J Pediatr Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: St. Louis, MO : Mosby |
| MeSH Terms: | Cardiotonic Agents/*pharmacology ; Pyridones/*pharmacology ; Shock, Septic/*drug therapy ; Vasodilator Agents/*pharmacology; Cardiotonic Agents/blood ; Cardiotonic Agents/pharmacokinetics ; Cardiotonic Agents/therapeutic use ; Hemodynamics/drug effects ; Pyridones/blood ; Pyridones/pharmacokinetics ; Pyridones/therapeutic use ; Shock, Septic/physiopathology ; Vasodilator Agents/blood ; Vasodilator Agents/pharmacokinetics ; Vasodilator Agents/therapeutic use ; Adolescent ; Child ; Child, Preschool ; Cross-Over Studies ; Double-Blind Method ; Half-Life ; Humans ; Infant ; Milrinone ; Prospective Studies |
| Abstract: | Objectives: The objectives of this study were to determine the pharmacokinetics of milrinone lactate in pediatric patients with septic shock and to determine whether a relationship exists between steady-state plasma milrinone concentrations and changes in hemodynamic variables.; Study Design: This was a randomized, double-blind, placebo-controlled, interventional study. In study phase 1 patients were randomized and underwent loading and infusion with milrinone lactate (50 microg/kg, then 0.5 microg/kg/min), and invasive hemodynamic values were determined. Steady-state was determined by obtaining plasma samples at 30, 15, and 0 minutes before the end of the milrinone infusion. Study phase 2 started when milrinone was discontinued by the patient care team. Steady-state was reaffirmed and plasma samples were obtained at 0.5, 1, 2, 4, 6, and 8 hours after the end of the infusion.; Results: The average plasma concentration at steady-state (Css avg) and total body clearance for phase 1 were 81.3+/-38.6 ng/ml (mean +/- SD) and 0.0106+/-0.0053 L/kg/min, respectively (n = 9). All but two patients underwent reloading with milrinone. In phase 2 Css avg and total body clearance were 65.8+/-42.1 ng/ml and 0.0110+/-0.0096 L/kg/min, respectively (n = 11). The average time of infusion was 51+/-21 hours. Eight patients were evaluated for phase 2 elimination. The mean elimination rate constant was 0.0091+/-0.0061 min(-1) (n = 8). The median half-life was 1.47 hours (range, 0.62 to 10.85 hours). All patients had creatinine clearances greater than 61 ml/min/1.73 m2. The volume of distribution at steady-state was 1.47+/-1.03 L/kg. No correlation existed between age and the elimination rate constant or the volume of distribution at steady-state. All patients achieved at least a 20% change in cardiac index and systemic vascular resistance index while maintaining a Css avg of 35 to 160 ng/ml. No adverse effects were noted. All patients achieved primary hemodynamic end points (cardiac index and systemic vascular resistance index) during the milrinone infusion.; Conclusions: Loading doses of 75 microg/kg milrinone lactate and starting infusion rates of 0.75 to 1.0 microg/kg/min for patients with normal renal function should be used; the infusion rate should then be titrated to effect. We recommend that for every increase of 0.25 microg/kg/min, a 25 microg/kg bolus dose be given. Because the median half-life is 1.47 hours, immediate hemodynamic effects may not be seen unless appropriate loading doses and infusion adjustments are made. |
| Substance Nomenclature: | 0 (Cardiotonic Agents); 0 (Pyridones); 0 (Vasodilator Agents); JU9YAX04C7 (Milrinone) |
| Entry Date(s): | Date Created: 19980320 Date Completed: 19980401 Latest Revision: 20190630 |
| Update Code: | 20260130 |
| DOI: | 10.1016/s0022-3476(98)70454-8 |
| PMID: | 9506650 |
| Database: | MEDLINE |
Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't