Browse > Article
http://dx.doi.org/10.24304/kjcp.2017.27.2.63

Contributing Factors on Pharmacokinetic Variability in Critically Ill Neonates  

An, Sook Hee (College of Pharmacy, Wonkwang University)
Publication Information
Korean Journal of Clinical Pharmacy / v.27, no.2, 2017 , pp. 63-68 More about this Journal
Abstract
Neonates have large inter-individual variability in pharmacokinetic parameters of many drugs due to developmental differences. The aim of this study was to investigate the factors affecting the pharmacokinetic parameters of drugs, which are commonly used in critically ill neonates. Factors that reflect physiologic maturation such as gestational age, postnatal age, postconceptional age, birth weight, and current body weight were correlated with pharmacokinetic parameters in neonates, especially preterm infants. Comorbidity characteristics affecting pharmacokinetics in critically ill neonates were perinatal asphyxia, hypoxic ischemic encephalopathy, patent ductus arteriosus (PDA), and renal dysfunction. Administration of indomethacin or ibuprofen in neonates with PDA was associated with the reduced clearance of renally excreted drugs such as vancomycin and amikacin. Therapeutic hypothermia and extracoporeal membrane oxygenation were influencing factors on pharmacokinetic parameters in critically ill neonates. Dosing adjustment and careful monitoring according to the factors affecting pharmacokinetic variability is required for safe and effective pharmacotherapy in neonatal intensive care unit.
Keywords
Neonates; neonatal intensive care unit; pharmacokinetics; preterm infants;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Zarfin Y, Koren G, Maresky D, Perlman M, MacLeod S. Possible indomethacin-aminoglycoside interaction in preterm infants. J Pediatr 1985;106(3):511-3.   DOI
2 Allegaert K. The impact of ibuprofen or indomethacin on renal drug clearance in neonates. J Matern Fetal Neonatal Med 2009;22(Suppl 3):88-91.   DOI
3 Matic M, Norman E, Rane A, et al. Effect of UGT2B7 -900G>A (-842G>A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort. Pharmacogenomics 2014;15(12):1589-97.   DOI
4 Friis-Hansen B. Water distribution in the foetus and newborn infant. Acta Peadiatr Scand Suppl 1983;305:7-11.
5 Pai VB, Nahata MC. Drug dosing in pediatric patients. In: Murphy JE, ed. Clinical pharmacokinetics. 5th ed. Bethesda, MD: Am Soc Healthsyst Pharm; 2011:29-44.
6 Vanpee M, Blennow M, Linne T, Herin P, Aperia A. Renal function in very low birth weight infants: normal maturity reached during early childhood. J Pediatr 1992;121:784-8.   DOI
7 Kearns GL. Pharmacogenetics and development: are infants and children at increased risk for adverse outcomes? Curr Opin Pediatr 1995;7:220-33.   DOI
8 Taketomo CK, Hodding JH, Kraus DM. Pediatric & Neonatal Dosage Handbook, 22th ed. Hudson, OH: Lexi-Comp, 2015
9 Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokinetics in newborns and infants. Clin Pharmacokinet 1980;5:485-527.   DOI
10 Besunder JB, Reed MD, Blumer JL. Principles of drug disposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface. Clin Pharmacokinet 1988;14:189-216   DOI
11 Friedman CA, Parks BR, Rawson JE. Gentamicin disposition in asphyxiated newborns: relationship to mean arterial pressure and urine output. Pediatr Pharmacol (New York)1982;2:189-97.
12 Touw DJ, Graafland O, Cranendonk A, Vermeulen RJ, van Weissenbruch MM. Clinical pharmacokinetics of phenobarbital in neonates. Eur J Pharm Sci 2000;12(2):111-6.   DOI
13 Marsot A, Brevaut-Malaty V, Vialet R, Boulamery A, Bruguerolle B, Simon N. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Fundam Clin Pharmacol 2014;28(4):465-71.   DOI
14 Donn SM, Grasela TH, Goldstein, GW. Safety of a Higher Loading Dose of Phenobarbital in the Term Newborn. Pediatrics 1985;75(6):1061-4.
15 Heimann G, Galdtke E. Pharmacokinetics of Phenobarbital in Childhood. Eur J Clin Pharmacol 1977;12(4):305-10.   DOI
16 Yukawa M, Yukawa E, Suematsu F, et al. Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. J Clin Pharm Ther 2011;36(6):704-10.   DOI
17 Lee SM, Chung JY, Lee YM, et al. Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures. Arch Dis Child 2012;97(6):569-72.   DOI
18 van den Broek MP, Groenendaal F, Toet MC, et al. Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach. Clin Pharmacokinet 2012;51(10):671-9.   DOI
19 Shellhaas RA, Ng CM, Dillon CH, Barks JD, Bhatt-Mehta V. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia. Pediatr Crit Care Med 2013;14(2):194-202.   DOI
20 Filippi L, la Marca G, Cavallaro G, et al. Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia. Epilepsia 2011;52(4):794-801.   DOI
21 Pitlick W, Painter M, Pippenger C. Phenobarbital pharmaockinetics in neonates. Clin P harmacol Ther 1978;23(3):346-50.   DOI
22 Grasela TH Jr, Donn SM. Neonatal population pharmacokinetics of phenobarbital derived from routine clinical data. Dev Pharmacol Ther 1985;8(6):374-83.   DOI
23 Kim SE, Kim BH, Lee S, et al. Population pharmacokinetics of theophylline in premature Korean infants. Ther Drug Monit 2013;35(3):338-44.   DOI
24 Fukuda T, Yukawa E, Kondo G, et al. Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea. J Clin Pharm Ther 2005;30(6):591-6.   DOI
25 Jones RA, Baillie E. Dosage schedule for intravenous aminophylline in apnoea of prematurity, based on pharmacokinetic studies. Arch Dis Child 1979;54(3):190-3.   DOI
26 Dothey CI, Tserng KY, Kaw S, King KC. Maturational changes of theophylline pharmacokinetics in preterm infants. Clin Pharmacol Ther 1989;45(5):461-8.   DOI
27 Aranda JV, Turmen T, Sasyniuk BI. Pharmacokinetics of diuretics and methylxanthines in the neonate. Eur J Clin Pharmacol 1980;18(1):55-63.   DOI
28 Moore ES, Faix RG, Banagale RC, Grasela TH. The population pharmacokinetics of theophylline in neonates and young infants. J Pharmacokinet Biopharm. 1989 Feb;17(1):47-66.   DOI
29 Brazier JL, Renaud H, Ribon B, Salle BL. Plasma xanthine levels in low birth weight infants treated or not treated with theophylline. Arch Dis Child 1979;54(3):194-9.   DOI
30 Islam SI, Ali AS, Sheikh AA, Fida NM. Pharmacokinetics of theophylline in preterm neonates during the first month of life. Saudi Med J 2004;25(4):459-65.
31 Young TE, Mangum B. Neofax. 24th ed. Thomson Reuters, 2011
32 Pacifici GM. Clinical pharmacokinetics of aminoglycosides in neonates: a review. Eur J Clin Pharmacol 2009;65:419-427.   DOI
33 Olavarria F, Dolz H, Krause S, et al. Torres T, Influence of gestational age and postnatal kidney maturation on the kinetics of gentamicin. Rev Chil Pediatr 1990;61(2):86-90.
34 An SH, Kim JY, Gwak HS. Outcomes of a new dosage regimen of amikacin based on pharmacokinetic parameters of Korean neonates. Am J Health-Syst Pharm 2014;71:122-7.   DOI
35 Treluyer JM, Merle Y, Tonnelier S, et al. Nonparametric population pharmacokinetic analysis of amikacin in neonates, infants and children. Antimicrob Agents Chemother 2002; 46:1381-7.   DOI
36 Allegaert K, Anderson BJ, Cossey V et al. Limited predictability of amikacin clearance in extreme premature neonates at birth. Br J Clin Pharmacol 2006;61:39-48.   DOI
37 Peterson PO, Wells TG, Kearns GL. Amikacin dosing in neonates: evaluation of a dosing chart based on population pharmacokinetic data. Dev Pharmacol Ther 1991;16:203-11.
38 Nielsen EI, Sandstrom M, Honore PH, Ewald U, Friberg LE. Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modeling of a prospective study. Clin Pharmacokinet 2009;48(4):253-63.   DOI
39 Lulic-Botica M, Sheer T, Edwards D, Thomas RL, Natarajan G. Impact of small-for-gestational age (SGA) status on gentamicin pharmacokinetics in neonates. J Clin Pharmacol 2014;54(1):39-45.   DOI
40 McDougal A, Ling EW, Levine M. Vancomycin pharmacokinetics and dosing in premature neonates. Ther Drug Monit 1995;17(4):319-26.   DOI
41 Radde IC. Renal function and elimination of drugs during development. In: Radde IC, Macleod SM, eds. Pediatric pharmacology and Therapeutics. St. Louis: Mosby-Tear Book. 1993;87.
42 deHoog M, Mouton JW, van den Anker JN. Vancomycin: pharmacokinetics and administration regimens in neonates. Clin Pharmacokinet 2004;43(7):417-40.   DOI
43 James A, Koren G, Milliken J, Soldin S, Prober C. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother 1987;31(1):52-4.   DOI
44 Jarrett RV, Marinkovich GA, Gayle EL, Bass JW. Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants. Pediatr Infect Dis J 1993;12(2):156-7.   DOI
45 Rodvold KA, Gentry CA, Plank GS, Kraus DM, Nickel E, Gross JR. Bayesian forecasting of serum vancomycin concentrations in neonates and infants. Ther Drug Monit 1995;17(3):239-46.   DOI
46 Rhodin MM, Anderson BJ, Peters AM, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol 2009; 24:67-76.   DOI
47 Kildoo CW, Lin LM, Gabriel MH, Folli HL, Modanlou HD. Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine. Dev Pharmacol Ther 1989;14(2):77-83.
48 Grimsley C, Thomson AH. Pharmacokinetics and dose requirements of vancomycin in neonates. Arch Dis Child Fetal Neonatal Ed 1999;81(3):F221-7.   DOI
49 Frymoyer A, Meng L, Bonifacio SL, Verotta D, Guglielmo BJ. Gentamicin pharmacokinetics and dosing in neonates with hypoxic ischemic encephalopathy receiving hypothermia. Pharmacotherapy 2013; 33(7):718-26.   DOI
50 Capparelli EV, Lane JR, Romanowski GL, et al. The influences of renal function and maturation on vancomycin elimination in newborns and infants. J Clin Pharmacol 2001;41(9):927-34.   DOI
51 Gilman JT, Gal P, Levine RS, Hersh CB, Erkain NV. Factors influencing theophylline disposition in 179 newborns. Ther Drug Monit 1986;8(1):4-10.   DOI
52 Gal P, Toback J, Erkan NV, Boer HR. The influence of asphyxia on phenobarbital dosing requirements in neonates. Dev Pharmacol Ther 1984;7(3):145-52.   DOI
53 Gal P, Boer HR, Toback J, Wells TJ, Erkan NV. Effect of asphyxia on theophylline clearance in newborns. South Med J 1982;75(7):836-8.   DOI
54 Friedman CA, Parks BR, Rawson JE. Gentamicin disposition in asphyxiated newborns: relationship to mean arterial blood pressure and urine output. Pediatr Pharmacol (New York) 1982;2(3):189-97.
55 Zanelli S, Buck M, Fairchild K. Physiologic and pharmacologic considerations for hypothermia therapy in neonates. J Perinatol 2011; 31(6):377-86.   DOI
56 Van den Broek MPH, Groenendaal F, Egberts ACG, et al. Effects of hypothermia on pharmacokinetics and pharmacodynamics. Clin Pharmacokin 2010; 49:277-94.   DOI
57 Mark LF, Solomon A, Northington FJ, Lee CK. Gentamicin pharmacokinetics in neonates undergoing therapeutic hypothermia. Ther Drug Monit 2013;35:217-22.   DOI
58 Ting JY, Kwan E, McDougal A, Osiovich H. Pharmacokinetics of gentamicin in newborns with moderate-to-severe hypoxicischemic encephalopathy undergoing therapeutic hypothermia. Ind J Pediatr 2015;82:119-25.   DOI
59 Bartlett RH, Gazzaniga AB, Toomasian J, Coran AG, Roloff D, Rucker R. Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg 1986;204(3):236-45.   DOI
60 Cies JJ, Fugarolas KN, Moore WS, Mason RW, Menkiti OR. Population Pharmacokinetics and Pharmacodynamic Target Attainment of Ampicillin in Neonates with Hypoxemic-Ischemic Encephalopathy in the Setting of Controlled Hypothermia. Pharmacotherapy 2017;37(4):456-63.   DOI
61 Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation; Implications for drug therapy of neonates. Clin Pharmacokinet 2003;42(5):403-17.   DOI
62 Marasco SF, Lukas G, McDonald M, McMillan J, Ihle B. Review of ECMO (extra corporeal membrane oxygenation) support in critically ill adult patients. Heart Lung Circ 2008;17(Suppl 4):S41-7.
63 Lawson G, Mulla H, Upton DR, Firmin RK. Drug disposition during extracorporeal membrane oxygenation (ECMO). Paediatric Perinatal Drug Ther 2001;4:109-20.
64 Cohen P, Collart L, Prober CG, Fischer AF, Blaschke TF. Gentamicin pharmacokinetics in neonates undergoing extracorporeal membrane oxygenation. Pediatr Infect Dis J 1990;9(8):562-6.   DOI
65 Dodge WF, JelliffeRW, Zwischenberger JB, Bellanger RA, Hokanson JA, Snodgrass WR. Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. Ther Drug Monit 1994;16(6):552-9.   DOI
66 Amaker RD, DiPiro JT, Bhatia J. Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 1996;40:1139-42.
67 Peters JW, Anderson BJ, Simons SH, Uges DR, Tibboel D. Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 2005;31:257-63.   DOI
68 Frymoyer A, Bonifacio SL, Drover DR, et al. Decreased Morphine Clearance in Neonates With Hypoxic Ischemic Encephalopathy Receiving Hypothermia. J Clin Pharmacol 2017;57(1):64-76.   DOI
69 Buck ML. Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 1998;18(5):1082-6.
70 Geiduschek JM, Lynn AM, Bratton SL, et al. Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation. Crit Care Med 1997;25:360-4.   DOI
71 Ahsman MJ, Hanekamp M, Wildschut ED, Tibboel D, Mathot RA. Population pharmacokinetics of midazolam and its metabolites during venoarterial extracorporeal membrane oxygenation in neonates. Clin Pharmacokinet 2010;49:407-19.   DOI
72 Ahsman MJ, Wildschut ED, Tibboel D, Mathot RA. Pharmacokinetics of cefotaxime and desacetylcefotaxime in infants during extracorporeal membrane oxygenation. Antimicrob Agents Chemother 2010; 54:1734-41.   DOI
73 Wildschut ED, Ahsman MJ, Houmes RJ, et al. Pharmacotherapy in neonatal and pediatric extracorporeal membrane oxygenation (ECMO). Curr Drug Metab 2012;13:767-77.   DOI
74 Williams BS, Ransom JL, Gap P, et al. Gentamicin pharmacokinetics in neonates with patent ductus arteriosus. Crit Care Med 1997;25:273-275.   DOI
75 Watterberg KL, Kelly HW, Johnson JD, Aldrich M, Angelus P. Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birth weight (less than 1,500 g) babies. Dev Pharmacol Ther 1987;10(2):107-17.   DOI
76 Touw DJ, Proost JH, Stevens R, Lafeber HN, van Weissenbruch MM. Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus. Pharm World Sci 2001;23(5):200-4.   DOI
77 Gal P, Ransom JL, Weaver RL. Gentamicin in neonates: the need for loading dose. Am J Perinatol 1990;7:254-7.   DOI