A population pharmacokinetic analysis of milrinone in pediatric patients after cardiac surgery

被引:56
作者
Bailey, JM [1 ]
Hoffman, TM
Wessel, DL
Nelson, DP
Atz, AM
Chang, AC
Kulik, TJ
Spray, TL
Akbary, A
Miller, RP
Wernovsky, G
机构
[1] Emory Univ, Sch Med, Atlanta, GA 30322 USA
[2] Anesthesia Associates Gainesville, NE Georgia Med Ctr, Dept Anesthesiol, Gainesville, FL USA
[3] Columbus Childrens Hosp, Columbus, OH USA
[4] Boston Childrens Hosp, Boston, MA USA
[5] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA
[6] Med Univ S Carolina, Charleston, SC 29425 USA
[7] Texas Childrens Hosp, Houston, TX 77030 USA
[8] Univ Michigan Hosp, Ann Arbor, MI 48109 USA
[9] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[10] Sanofi Synthelabo Inc, New York, NY USA
关键词
congenital heart disease; phosphodiesterase inhibitors; milrinone; pharmacokinetics; mixed-effects modeling;
D O I
10.1023/B:JOPA.0000029488.45177.48
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
The purpose of this study was to ascertain the optimal pharmacokinetic model for milrinone in pediatric patients after cardiac surgery when milrinone was administered as a slow loading dose followed by a constant-rate infusion. The data used for pharmacokinetic analysis were collected in a prospective, randomized, placebo-controlled multi-center trial of milrinone as prophylaxis for the development of low cardiac output syndrome after surgery for repair of complex congenital cardiac defects. Two blood samples were randomly collected from each patient for determination of plasma milrinone concentrations with subsequent population pharmacokinetic modeling. The pharmacokinetics of milrinone in pediatric patients under 6 year's age were best described by a weight-normalized one compartment model after a slow loading dose followed by a constant-rate infusion. The volume of distribution was 482 ml kg(-1), and was independent of age. Clearance was a linear function of age given by Cl = 2.42 ml kg(-1) min(-1) [1 + 0.0396* age].
引用
收藏
页码:43 / 59
页数:17
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