Abstract
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 6year'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 482mlkg−1, and was independent of age. Clearance was a linear function of age given by Cl=2.42mlkg−1min−1[1+0.0396*age].
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REFERENCES
G.¡V.¡S.¡ Parr,¡E.¡H.¡ Blackstone,¡and¡J.¡W.¡ Kirklin.¡Cardiac¡performance¡and¡mortality¡early¡after¡intracardiac¡surgery¡in¡infants¡and¡young¡children.¡Circulation¡51:867-874¡(1975).
F.¡A.¡ Burrows,¡W.¡G.¡ Williams,¡K.¡H.¡ Teoh,¡A.¡E.¡ Wood,¡J.¡ Burns,¡J.¡ Edmonds,¡G.¡A.¡ Barker,¡G.¡A.¡ Trusler,¡and¡R.¡D.¡ Weisel.¡Myocardial¡performance¡after¡repair¡of¡congenital¡cardiac¡defects¡in¡infants¡and¡children.¡J.¡Thorac.¡Cardiovasc.¡Surg.¡96:548-556¡(1988).
G.¡ Wernovsky,¡D.¡ Wypij,¡R.¡A.¡ Jonas,¡J.¡E.¡ Mayer,¡F.¡L.¡ Hanley,¡P.¡R.¡ Hickey,¡A.¡L.¡ Walsh,¡A.¡C.¡ Chang,¡A.¡R.¡ Casteneda,¡and¡J.¡W.¡ Newburger.¡Postoperative¡course¡and¡hemodynamic¡profile¡after¡the¡arterial¡switch¡operation¡in¡neonates¡and¡infants.¡A¡comparison¡of¡low-flow¡cardiopulmonary¡bypass¡and¡circulatory¡arrest.¡Circulation¡92:2226-2235¡(1995).
C.¡ Ramamoorthy,¡G.¡D.¡ Anderson,¡G.¡D.¡ Williams,¡and¡A.¡M.¡ Lynn.¡Pharmacokinetics¡and¡side¡effects¡of¡milrinone¡in¡infants¡and¡children¡after¡open¡heart¡surgery.¡Anesth¡Analg¡86:283-289¡(1998).
J.¡M.¡ Bailey,¡B.¡E.¡ Miller,¡W.¡ Lu,¡S.¡R.¡ Tosone,¡K.¡R.¡ Kanter,¡and¡V.¡K.¡ Tam.¡The¡pharmacokinetics¡and¡pharmacodynamics¡of¡milrinone¡in¡pediatric¡patients¡after¡cardiac¡surgery.¡Anesthesiology¡90:1012-1018¡(1999).
T.¡M.¡ Hoffman,¡G.¡ Wernovsky,¡A.¡M.¡ Atz,¡J.¡M.¡ Bailey,¡A.¡ Akbary,¡J.¡F.¡ Kocsis,¡D.¡P.¡ Nelson,¡A.¡C.¡ Chang,¡T.¡J.¡ Kulik,¡T.¡L.¡ Spray,¡and¡D.¡L.¡I.¡ Wessel.¡Prophylactic¡intravenous¡use¡of¡milrinone¡after¡cardiac¡operations¡in¡pediatrics¡(PRIMACORP)¡study.¡Am.¡Heart.¡J.¡143:15-21¡(2002).
T.¡M.¡ Hoffman,¡G.¡ Wernovsky,¡A.¡ Atz,¡T.¡J.¡ Kulik,¡D.¡P.¡ Nelson,¡A.¡C.¡ Chang,¡J.¡M.¡ Bailey,¡A.¡ Akbary,¡J.¡F.¡ Kocsis,¡R.¡ Kaczmarek,¡T.¡L.¡ Spray,¡and¡D.¡L.¡I.¡ Wessel.¡Efficacy¡and¡safety¡of¡milrinone¡in¡preventing¡low¡cardiac¡output¡syndrome¡in¡infants¡and¡children¡after¡corrective¡surgery¡for¡congenital¡heart¡disease.¡Circulation¡107:996-1002¡(2003).
J.¡ Edelson,¡R.¡F.¡ Koss,¡R.¡F.¡ Baker,¡and¡G.¡B.¡ Park.¡High-performance¡chromatographic¡analysis¡of¡milrinone¡in¡plasma¡and¡urine.¡Intravenous¡pharmacokinetics¡in¡the¡dog.¡Chromatogr.276:456-462¡(1983).
S.¡ Beal¡and¡L.¡ Sheiner.¡NONMEM¡User's¡Guide.¡San¡Francisco,¡University¡of¡California,¡1992.
M.¡ Davidian¡and¡D.¡M.¡ Giltinan.¡Nonlinear¡Models¡for¡Repeated¡Measurement¡Data.¡Chapman¡and¡Hall,¡Boca¡Raton,¡1995.
N.¡H.¡G.¡ Holford.¡A¡size¡standard¡for¡pharmacokinetics.¡Clin.¡Pharmacokinet.¡30:329-332¡(1996).
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Bailey, J.M., Hoffman, T.M., Wessel, D.L. et al. A Population Pharmacokinetic Analysis of Milrinone in Pediatric Patients After Cardiac Surgery. J Pharmacokinet Pharmacodyn 31, 43–59 (2004). https://doi.org/10.1023/B:JOPA.0000029488.45177.48
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DOI: https://doi.org/10.1023/B:JOPA.0000029488.45177.48