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Population Pharmacokinetic Analysis during the First 2 Years of Life

An Overview

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Abstract

Three decades after its introduction, pharmacokinetic population approaches have become a reference method for drug modelling, particularly in paediatrics. The main practical limitation in this specific population is the collected blood volume. Pharmacokinetic population approaches using sparse sampling may resolve this issue. The pharmacokinetics of many drugs have been studied during the last 25 years using such methods. This review summarizes all of the published studies concerning population pharmacokinetic approaches in paediatric subjects from neonate to 2 years old. A literature search was conducted using the PubMed database, from 1985 to December 2010, using the following terms: pharmacokinetic(s), population, paediatric/pediatric and neonate(s). Articles were excluded if they were not pertinent according to our criteria. References of all relevant articles were also evaluated. Ninety-eight studies were included in this review. The following information was extracted from the articles: drug name, therapeutic class, population size, age of patients, number of samples per patient, covariates used for clearance and volume of distribution estimates, software used for modelling and validation methods. An increasing rate of publications over the years was observed; 44 different drugs were studied using a pharmacokinetic population approach. Antibacterials were the most studied class of drugs, including a large number of studies devoted to vancomycin and gentamicin. It must be underlined that few studies have been performed on anticonvulsant drugs and anaesthetics used in clinical daily practice conditions.

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References

  1. Steinbrook R. Testing medications in children. N Engl J Med. 2002;347:1462–70.

    Article  PubMed  Google Scholar 

  2. Rosato J. The ethics of clinical trials: a child’s view. J Law Med Ethics. 2000;28:362–78.

    Article  CAS  PubMed  Google Scholar 

  3. Conroy S, Choonara I, Impicciatore P, et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. BMJ. 2000;320:79–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Treluyer JM, Berger JF, Leclerc F, et al. Use of off-label and unlicensed drugs in neonatal and paediatric intensive care in France [abstract no. 46A]. Pediatric Academic Societies Annual Meeting; 1–4 May 1999; San Francisco.

  5. Chalumeau M, Treluyer JM, Salenave B, et al. Off label and unlicensed drug use among office-based paediatricians. Arch Dis Child. 2000;82:502–5.

    Article  Google Scholar 

  6. Anderson GD, Lynn AM. Optimizing pediatric dosing: a developmental pharmacologic approach. Pharmacotherapy. 2009;29(6):680–90.

    Article  CAS  PubMed  Google Scholar 

  7. Anderson BJ. My child is unique; the pharmacokinetics are universal. Paediatr Anaesth. 2012;22(6):530–8.

    Article  PubMed  Google Scholar 

  8. Brendel K, Dartois C, Comets E, Lemenuel-Diot A, Laveille C, Tranchand B, et al. Are population pharmacokinetic and/or pharmacodynamic models adequately evaluated? A survey of the literature from 2002 to 2004. Clin Pharmacokinet. 2007;46(3):221–34.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Tod M, Jullien V, Pons G. Facilitation of drug evaluation in children by population methods and modelling. Clin Pharmacokinet. 2008;47(4):231–43.

    Article  CAS  PubMed  Google Scholar 

  10. Grasela TH Jr, Donn SM. Neonatal population pharmacokinetics of phenobarbital derived from routine clinical data. Dev Pharmacol Ther. 1985;8(6):374–83.

    PubMed  Google Scholar 

  11. Schaible DH, Rocci ML Jr, Alpert GA, Campos JM, Paul MH, Polin RA, et al. Vancomycin pharmacokinetics in infants: relationships to indices of maturation. Pediatr Infect Dis. 1986;5(3):304–8.

    Article  CAS  PubMed  Google Scholar 

  12. Thomson AH, Way S, Bryson SM, McGovern EM, Kelman AW, Whiting B. Population pharmacokinetics of gentamicin in neonates. Dev Pharmacol Ther. 1988;11(3):173–9.

    CAS  PubMed  Google Scholar 

  13. Moore ES, Faix RG, Banagale RC, Grasela TH. The population pharmacokinetics of theophylline in neonates and young infants. J Pharmacokinet Biopharm. 1989;17(1):47–66.

    Article  CAS  PubMed  Google Scholar 

  14. Wiest DB, Pinson JB, Gal PS, Brundage RC, Schall S, Ransom JL, et al. Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus. Clin Pharmacol Ther. 1991;49(5):550–7.

    Article  CAS  PubMed  Google Scholar 

  15. Karlsson MO, Thomson AH, McGovern EM, Chow P, Evans TJ, Kelman AW. Population pharmacokinetics of rectal theophylline in neonates. Ther Drug Monit. 1991;13(3):195–200.

    Article  CAS  PubMed  Google Scholar 

  16. Fattinger K, Vozeh S, Olafsson A, Vlcek J, Wenk M, Follath F. Netilmicin in the neonate: population pharmacokinetic analysis and dosing recommendations. Clin Pharmacol Ther. 1991;50(1):55–65.

    Article  CAS  PubMed  Google Scholar 

  17. Izquierdo M, Lanao JM, Cervero L, Jimenez NV, Domínguez-Gil A. Population pharmacokinetics of gentamicin in premature infants. Ther Drug Monit. 1992;14(3):177–83.

    Article  CAS  PubMed  Google Scholar 

  18. Jensen PD, Edgren BE, Brundage RC. Population pharmacokinetics of gentamicin in neonates using a nonlinear, mixed-effects model. Pharmacotherapy. 1992;12(3):178–82.

    CAS  PubMed  Google Scholar 

  19. Karna P, Lee C, Kumar A, Dyke J, Gooch WM 3rd. Population pharmacokinetics of ceftizoxime in premature newborns. Dev Pharmacol Ther. 1993;20(3–4):135–43.

    CAS  PubMed  Google Scholar 

  20. Weber W, Kewitz G, Rost KL, Looby M, Nitz M, Harnisch L. Population kinetics of gentamicin in neonates. Eur J Clin Pharmacol. 1993;44(Suppl 1):S23–5.

    Article  PubMed  Google Scholar 

  21. Asbury WH, Darsey EH, Rose WB, Murphy JE, Buffington DE, Capers CC. Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation. Ann Pharmacother. 1993;27(4):490–6.

    Article  CAS  PubMed  Google Scholar 

  22. Burtin P, Jacqz-Aigrain E, Girard P, Lenclen R, Magny JF, Betremieux P, et al. Population pharmacokinetics of midazolam in neonates. Clin Pharmacol Ther. 1994;56(6 Pt 1):615–25.

    Article  CAS  PubMed  Google Scholar 

  23. Seay RE, Brundage RC, Jensen PD, Schilling CG, Edgren BE. Population pharmacokinetics of vancomycin in neonates. Clin Pharmacol Ther. 1994;56(2):169–75.

    Article  CAS  PubMed  Google Scholar 

  24. Lee TC, Charles BG, Steer PA, Flenady VJ, Grant TC. Theophylline population pharmacokinetics from routine monitoring data in very premature infants with apnoea. Br J Clin Pharmacol. 1996;41(3):191–200.

    Article  CAS  PubMed  Google Scholar 

  25. Zhou XJ, Gruber W, Demmler G, Jacobs R, Reuman P, Adler S, et al. Population pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections: NIAID Collaborative Antiviral Study Group. Antimicrob Agents Chemother. 1996;40(9):2202–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Thomson AH, Kerr S, Wright S. Population pharmacokinetics of caffeine in neonates and young infants. Ther Drug Monit. 1996;18(3):245–53.

    Article  CAS  PubMed  Google Scholar 

  27. Harte GJ, Gray PH, Lee TC, Steer PA, Charles BG. Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates. J Paediatr Child Health. 1997;33(4):335–8.

    Article  CAS  PubMed  Google Scholar 

  28. Charles BG, Preechagoon Y, Lee TC, Steer PA, Flenady VJ, Debuse N. Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants. J Pharm Sci. 1997;86(11):1288–92.

    Article  CAS  PubMed  Google Scholar 

  29. de Hoog M, Schoemaker RC, Mouton JW, van den Anker JN. Tobramycin population pharmacokinetics in neonates. Clin Pharmacol Ther. 1997;62(4):392–9.

    Article  PubMed  Google Scholar 

  30. Falcão AC, de Fernández Gatta MM, Delgado Iribarnegaray MF, Santos Buelga D, García MJ, Dominguez-Gil A, et al. Population pharmacokinetics of caffeine in premature neonates. Eur J Clin Pharmacol. 1997;52(3):211–7.

    Article  PubMed  Google Scholar 

  31. Lee TC, Charles B, Steer P, Flenady V, Shearman A. Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity. Clin Pharmacol Ther. 1997;61(6):628–40.

    Article  CAS  PubMed  Google Scholar 

  32. Botha JH, du Preez MJ, Miller R, Adhikari M. Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models. Eur J Clin Pharmacol. 1998;53(5):337–41.

    Article  CAS  PubMed  Google Scholar 

  33. Yasuhara M, Iga T, Zenda H, Okumura K, Oguma T, Yano Y, Hori R. Population pharmacokinetics of vancomycin in Japanese pediatric patients. Ther Drug Monit. 1998;20(6):612–8.

    Article  CAS  PubMed  Google Scholar 

  34. Silva R, Reis E, Bispo MA, Almeida AM, Costa IM, Falcão F, et al. The kinetic profile of vancomycin in neonates. J Pharm Pharmacol. 1998;50(11):1255–60.

    Article  CAS  PubMed  Google Scholar 

  35. Lee TC, Charles BG, Harte GJ, Gray PH, Steer PA, Flenady VJ. Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics. Anesthesiology. 1999;90(2):451–7.

    Article  CAS  PubMed  Google Scholar 

  36. du Preez MJ, Botha JH, McFadyen ML, Holford NH. The pharmacokinetics of theophylline in premature neonates during the first few days after birth. Ther Drug Monit. 1999;21(6):598–603.

    Article  PubMed  Google Scholar 

  37. Vervelde ML, Rademaker CM, Krediet TG, Fleer A, van Asten P, van Dijk A. Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen. Ther Drug Monit. 1999;21(5):514–9.

    Article  CAS  PubMed  Google Scholar 

  38. Grimsley C, Thomson AH. Pharmacokinetics and dose requirements of vancomycin in neonates. Arch Dis Child Fetal Neonatal Ed. 1999;81(3):F221–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Preechagoon Y, Charles B, Piotrovskij V, Donovan T, Van Peer A. Population pharmacokinetics of enterally administered cisapride in young infants with gastro-oesophageal reflux disease. Br J Clin Pharmacol. 1999;48(5):688–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mirochnick M, Capparelli E, Connor J. Pharmacokinetics of zidovudine in infants: a population analysis across studies. Clin Pharmacol Ther. 1999;66(1):16–24.

    Article  CAS  PubMed  Google Scholar 

  41. Wang J, Liang WQ, Wu JJ, Pan CM. Population pharmacokinetic analysis of amikacin and validation on neonates using Monte Carlo method. Acta Pharmacol Sin. 2000;21(10):954–60.

    CAS  PubMed  Google Scholar 

  42. de Hoog M, Schoemaker RC, Mouton JW, van den Anker JN. Vancomycin population pharmacokinetics in neonates. Clin Pharmacol Ther. 2000;67(4):360–7.

    Article  PubMed  Google Scholar 

  43. Hansen TG, Ilett KF, Reid C, Lim SI, Hackett LP, Bergesio R. Caudal ropivacaine in infants: population pharmacokinetics and plasma concentrations. Anesthesiology. 2001;94(4):579–84.

    Article  CAS  PubMed  Google Scholar 

  44. Bleyzac N, Varnier V, Labaune JM, Corvaisier S, Maire P, Jelliffe RW, et al. Population pharmacokinetics of amikacin at birth and interindividual variability in renal maturation. Eur J Clin Pharmacol. 2001;57(6–7):499–504.

    CAS  PubMed  Google Scholar 

  45. Kimura T, Kokubun H, Nowatari M, Matsuura N, Sunakawa K, Kubo H. Population pharmacokinetics of panipenem in neonates and retrospective evaluation of dosage. J Antimicrob Chemother. 2001;47(1):51–9.

    Article  CAS  PubMed  Google Scholar 

  46. Falcão AC, Buelga DS, Méndez ME, García MJ, Pardo M. Population kinetics of tobramycin in neonates. Ther Drug Monit. 2001;23(3):202–8.

    Article  PubMed  Google Scholar 

  47. Capparelli EV, Lane JR, Romanowski GL, McFeely EJ, Murray W, Sousa P, et al. The influences of renal function and maturation on vancomycin elimination in newborns and infants. J Clin Pharmacol. 2001;41(9):927–34.

    Article  CAS  PubMed  Google Scholar 

  48. Tod M, Lokiec F, Bidault R, De Bony F, Petitjean O, Aujard Y. Pharmacokinetics of oral acyclovir in neonates and in infants: a population analysis. Antimicrob Agents Chemother. 2001;45(1):150–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Suematsu F, Yukawa E, Yukawa M, Minemoto M, Ohdo S, Higuchi S, et al. Population-based investigation of relative clearance of digoxin in Japanese neonates and infants by multiple-trough screen analysis. Eur J Clin Pharmacol. 2001;57(1):19–24.

    Article  CAS  PubMed  Google Scholar 

  50. Stolk LM, Degraeuwe PL, Nieman FH, de Wolf MC, de Boer A. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates. Ther Drug Monit. 2002;24(4):527–31.

    Article  CAS  PubMed  Google Scholar 

  51. de Hoog M, Schoemaker RC, van den Anker JN, Vinks AA. NONMEM and NPEM2 population modeling: a comparison using tobramycin data in neonates. Ther Drug Monit. 2002;24(3):359–65.

    Article  PubMed  Google Scholar 

  52. Odoul F, Le Guellec C, Henrot A, Saliba E, Levron JC, Saux MC, et al. Population pharmacokinetics of cisapride in neonates. Eur J Clin Pharmacol. 2002;58(8):507–13.

    Article  CAS  PubMed  Google Scholar 

  53. Mulla H, McCormack P, Lawson G, Firmin RK, Upton DR. Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation. Anesthesiology. 2003;99(2):275–82.

    Article  CAS  PubMed  Google Scholar 

  54. Botha JH, du Preez MJ, Adhikari M. Population pharmacokinetics of gentamicin in South African newborns. Eur J Clin Pharmacol. 2003;59(10):755–9.

    Article  CAS  PubMed  Google Scholar 

  55. DiCenzo R, Forrest A, Slish JC, Cole C, Guillet R. A gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates. Pharmacotherapy. 2003;23(5):585–91.

    Article  CAS  PubMed  Google Scholar 

  56. Gregoire N, Gualano V, Geneteau A, Millerioux L, Brault M, Mignot A, et al. Population pharmacokinetics of ibuprofen enantiomers in very premature neonates. J Clin Pharmacol. 2004;44(10):1114–24.

    Article  CAS  PubMed  Google Scholar 

  57. Smyth JM, Collier PS, Darwish M, Millership JS, Halliday HL, Petersen S, et al. Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus: a population pharmacokinetic study. Br J Clin Pharmacol. 2004;58(3):249–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bouwmeester NJ, Anderson BJ, Tibboel D, Holford NH. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. Br J Anaesth. 2004;92(2):208–17.

    Article  CAS  PubMed  Google Scholar 

  59. Rapp HJ, Molnár V, Austin S, Krohn S, Gädeke V, Motsch J, et al. Ropivacaine in neonates and infants: a population pharmacokinetic evaluation following single caudal block. Paediatr Anaesth. 2004;14(9):724–32.

    Article  PubMed  Google Scholar 

  60. Allegaert K, Anderson BJ, Naulaers G, de Hoon J, Verbesselt R, Debeer A, et al. Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm neonates. Eur J Clin Pharmacol. 2004;60(3):191–7.

    Article  CAS  PubMed  Google Scholar 

  61. Kimura T, Sunakawa K, Matsuura N, Kubo H, Shimada S, Yago K. Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates. Antimicrob Agents Chemother. 2004;48(4):1159–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lanao JM, Calvo MV, Mesa JA, Martín-Suárez A, Carbajosa MT, Miguelez F, et al. Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates. J Antimicrob Chemother. 2004;54(1):193–8.

    Article  CAS  PubMed  Google Scholar 

  63. Bailey JM, Hoffman TM, Wessel DL, Nelson DP, Atz AM, Chang AC, et al. A population pharmacokinetic analysis of milrinone in pediatric patients after cardiac surgery. J Pharmacokinet Pharmacodyn. 2004;31(1):43–59.

    Article  CAS  PubMed  Google Scholar 

  64. Chalkiadis GA, Anderson BJ, Tay M, Bjorksten A, Kelly JJ. Pharmacokinetics of levobupivacaine after caudal epidural administration in infants less than 3 months of age. Br J Anaesth. 2005;95(4):524–9.

    Article  CAS  PubMed  Google Scholar 

  65. Fukuda T, Yukawa E, Kondo G, Maeda T, Shin-o T, Kondo Y, et al. Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea. J Clin Pharm Ther. 2005;30(6):591–6.

    Article  CAS  PubMed  Google Scholar 

  66. Capparelli E, Hochwald C, Rasmussen M, Parham A, Bradley J, Moya F. Population pharmacokinetics of cefepime in the neonate. Antimicrob Agents Chemother. 2005;49(7):2760–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yukawa E, Suematsu F, Yukawa M, Minemoto M. Population pharmacokinetic investigation of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants. J Clin Pharm Ther. 2005;30(2):159–63.

    Article  CAS  PubMed  Google Scholar 

  68. Würthwein G, Groll AH, Hempel G, Adler-Shohet FC, Lieberman JM, Walsh TJ. Population pharmacokinetics of amphotericin B lipid complex in neonates. Antimicrob Agents Chemother. 2005;49(12):5092–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Pullen J, Stolk LM, Nieman FH, Degraeuwe PL, van Tiel FH, Zimmermann LJ. Population pharmacokinetics and dosing of amoxicillin in (pre)term neonates. Ther Drug Monit. 2006;28(2):226–31.

    Article  CAS  PubMed  Google Scholar 

  70. Pullen J, de Rozario L, Stolk LM, Degraeuwe PL, van Tiel FH, Zimmermann LJ. Population pharmacokinetics and dosing of flucloxacillin in preterm and term neonates. Ther Drug Monit. 2006;28(3):351–8.

    Article  CAS  PubMed  Google Scholar 

  71. García B, Barcia E, Pérez F, Molina IT. Population pharmacokinetics of gentamicin in premature newborns. J Antimicrob Chemother. 2006;58(2):372–9.

    Article  PubMed  Google Scholar 

  72. Al Z’aabi M, Lanner A, Xiaonian X, Donovan T, Charles B. Application of routine monitoring data for determination of the population pharmacokinetics and enteral bioavailability of phenytoin in neonates and infants with seizures. Ther Drug Monit. 2006;28(6):793–9.

    Article  CAS  Google Scholar 

  73. Zuppa AF, Nicolson SC, Adamson PC, Wernovsky G, Mondick JT, Burnham N, et al. Population pharmacokinetics of milrinone in neonates with hypoplastic left heart syndrome undergoing stage I reconstruction. Anesth Analg. 2006;102(4):1062–9.

    Article  CAS  PubMed  Google Scholar 

  74. van Kesteren C, Benders MJ, Groenendaal F, van Bel F, Ververs FF, Rademaker CM. Population pharmacokinetics of allopurinol in full-term neonates with perinatal asphyxia. Ther Drug Monit. 2006;28(3):339–44.

    Article  PubMed  CAS  Google Scholar 

  75. Al Za’abi M, Donovan T, Tudehope D, Woodgate P, Collie LA, Charles B. Orogastric and intravenous indomethacin administration to very premature neonates with patent ductus arteriosus: population pharmacokinetics, absolute bioavailability, and treatment outcome. Ther Drug Monit. 2007;29(6):807–14.

    Article  PubMed  CAS  Google Scholar 

  76. Allegaert K, Peeters MY, Verbesselt R, Tibboel D, Naulaers G, de Hoon JN, et al. Inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Br J Anaesth. 2007;99(6):864–70.

    Article  CAS  PubMed  Google Scholar 

  77. Muller AE, DeJongh J, Bult Y, Goessens WH, Mouton JW, Danhof M, et al. Pharmacokinetics of penicillin G in infants with a gestational age of less than 32 weeks. Antimicrob Agents Chemother. 2007;51(10):3720–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Anderson BJ, Allegaert K, Van den Anker JN, Cossey V, Holford NH. Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol. 2007;63(1):75–84.

    Article  CAS  PubMed  Google Scholar 

  79. Acosta EP, Brundage RC, King JR, Sánchez PJ, Sood S, Agrawal V, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, et al. Ganciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation. Clin Pharmacol Ther. 2007;81(6):867–72.

    Article  CAS  PubMed  Google Scholar 

  80. Yukawa E, Akiyama K, Suematsu F, Yukawa M, Minemoto M. Population pharmacokinetic investigation of digoxin in Japanese neonates. J Clin Pharm Ther. 2007;32(4):381–6.

    Article  CAS  PubMed  Google Scholar 

  81. Paradisis M, Jiang X, McLachlan AJ, Evans N, Kluckow M, Osborn D. Population pharmacokinetics and dosing regimen design of milrinone in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2007;92(3):F204–9.

    Article  PubMed  Google Scholar 

  82. Hirt D, Van Overmeire B, Treluyer JM, Langhendries JP, Marguglio A, Eisinger MJ, et al. An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study. Br J Clin Pharmacol. 2008;65(5):629–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Gregoire N, Desfrere L, Roze JC, Kibleur Y, Koehne P. Population pharmacokinetic analysis of Ibuprofen enantiomers in preterm newborn infants. J Clin Pharmacol. 2008;48(12):1460–8.

    Article  CAS  PubMed  Google Scholar 

  84. Palmer GM, Atkins M, Anderson BJ, Smith KR, Culnane TJ, McNally CM, et al. I.V. acetaminophen pharmacokinetics in neonates after multiple doses. Br J Anaesth. 2008;101(4):523–30.

    Article  CAS  PubMed  Google Scholar 

  85. Lima-Rogel V, Medina-Rojas EL, Del Carmen Milán-Segovia R, Noyola DE, Nieto-Aguirre K, López-Delarosa A, et al. Population pharmacokinetics of cefepime in neonates with severe nosocomial infections. J Clin Pharm Ther. 2008;33(3):295–306.

    Article  CAS  PubMed  Google Scholar 

  86. Bradley JS, Sauberan JB, Ambrose PG, Bhavnani SM, Rasmussen MR, Capparelli EV. Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate. Pediatr Infect Dis J. 2008;27(9):794–9.

    Article  PubMed  Google Scholar 

  87. Wade KC, Wu D, Kaufman DA, Ward RM, Benjamin DK Jr. Sullivan JE, et al. National Institute of Child Health and Development Pediatric Pharmacology Research Unit Network. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother. 2008;52(11):4043–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Charles BG, Townsend SR, Steer PA, Flenady VJ, Gray PH, Shearman A. Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther Drug Monit. 2008;30(6):709–16.

    Article  CAS  PubMed  Google Scholar 

  89. Dailly E, Drouineau MH, Gournay V, Rozé JC, Jolliet P. Population pharmacokinetics of domperidone in preterm neonates. Eur J Clin Pharmacol. 2008;64(12):1197–200.

    Article  CAS  PubMed  Google Scholar 

  90. Zuppa AF, Mondick JT, Davis L, Cohen D. Population pharmacokinetics of ketorolac in neonates and young infants. Am J Ther. 2009;16(2):143–6.

    Article  PubMed  Google Scholar 

  91. Sherwin CM, Svahn S, Van der Linden A, Broadbent RS, Medlicott NJ, Reith DM. Individualised dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis. Eur J Clin Pharmacol. 2009;65(7):705–13.

    Article  CAS  PubMed  Google Scholar 

  92. Nielsen EI, Sandström M, Honoré PH, Ewald U, Friberg LE. Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study. Clin Pharmacokinet. 2009;48(4):253–63.

    Article  CAS  PubMed  Google Scholar 

  93. van den Anker JN, Pokorna P, Kinzig-Schippers M, Martinkova J, de Groot R, Drusano GL, et al. Meropenem pharmacokinetics in the newborn. Antimicrob Agents Chemother. 2009;53(9):3871–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Mukherjee A, Dombi T, Wittke B, Lalonde R. Population pharmacokinetics of sildenafil in term neonates: evidence of rapid maturation of metabolic clearance in the early postnatal period. Clin Pharmacol Ther. 2009;85(1):56–63.

    Article  CAS  PubMed  Google Scholar 

  95. Hirt D, Urien S, Rey E, Arrivé E, Ekouévi DK, Coffié P, et al. Population pharmacokinetics of emtricitabine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Antimicrob Agents Chemother. 2009;53(3):1067–73.

    Article  CAS  PubMed  Google Scholar 

  96. Hirt D, Urien S, Ekouévi DK, Rey E, Arrivé E, Blanche S, et al. ANRS 12109. Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109). Clin Pharmacol Ther. 2009;85(2):182–9.

    Article  CAS  PubMed  Google Scholar 

  97. 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(6):407–19.

    Article  CAS  PubMed  Google Scholar 

  98. Marqués-Miñana MR, Saadeddin A, Peris JE. Population pharmacokinetic analysis of vancomycin in neonates: a new proposal of initial dosage guideline. Br J Clin Pharmacol. 2010;70(5):713–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Lo YL, van Hasselt JG, Heng SC, Lim CT, Lee TC, Charles BG. Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination. Antimicrob Agents Chemother. 2010;54(6):2626–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Hope WW, Smith PB, Arrieta A, Buell DN, Roy M, Kaibara A, et al. Population pharmacokinetics of micafungin in neonates and young infants. Antimicrob Agents Chemother. 2010;54(6):2633–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Blumer J, Rodriguez A, Sánchez PJ, Sallas W, Kaiser G, Hamed K. Single-dose pharmacokinetics of famciclovir in infants and population pharmacokinetic analysis in infants and children. Antimicrob Agents Chemother. 2010;54(5):2032–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Xie HG, Cao YJ, Gauda EB, Agthe AG, Hendrix CW, Lee H. Clonidine clearance matures rapidly during the early postnatal period: a population pharmacokinetic analysis in newborns with neonatal abstinence syndrome. J Clin Pharmacol. 2011;51(4):502–11.

    Article  CAS  PubMed  Google Scholar 

  103. Ward RM, Tammara B, Sullivan SE, Stewart DL, Rath N, Meng X, et al. Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD). Eur J Clin Pharmacol. 2010;66(6):555–61.

    Article  CAS  PubMed  Google Scholar 

  104. Benaboud S, Ekouévi DK, Urien S, Rey E, Arrivé E, Blanche S, TEmAA ANRS 12109 Study Group, et al. Population pharmacokinetics of nevirapine in HIV-1-infected pregnant women and their neonates. Antimicrob Agents Chemother. 2011;55(1):331–7.

    Article  CAS  PubMed  Google Scholar 

  105. Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children: a reappraisal. Clin Pharmacokinet. 1989;17:29–67.

    Article  PubMed  Google Scholar 

  106. Anderson BJ, Allegaert K, Holford NH. Population clinical pharmacology of children: modelling covariate effects. Eur J Pediatr. 2006;165:819–29.

    Article  PubMed  Google Scholar 

  107. West GB, Brown JH, Enquist BJ. The fourth dimension of life: fractal geometry and allometric scaling of organisms. Science. 1999;284(5420):1677–9.

    Article  CAS  PubMed  Google Scholar 

  108. Anderson BJ, Holford NH. Mechanistic basic of using body size and maturation to predict clearance in humans. Drug Metab Pharmacokinet. 2009;24(1):25–36.

    Article  CAS  PubMed  Google Scholar 

  109. Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Cole M, Chatelut E, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol. 2009;24(1):67–76.

    Article  PubMed  Google Scholar 

  110. World Health Organization. WHO model lists of essential medicines. http://whqlibdoc.who.int/hq/2011/a95964_fre.pdf. Accessed 1 Oct 2010.

  111. Jacqz-Aigrain E, Burtin P. Clinical pharmacokinetics of sedatives in neonates. Clin Pharmacokinet. 1996;31(6):423–43.

    Article  CAS  PubMed  Google Scholar 

  112. Rennie JM, Boylan GB. Neonatal seizures and their treatment. Curr Opin Neurol. 2003;6(2):177–81.

    Article  Google Scholar 

  113. Painter MJ, Pippenger C, Wasterlain C, Barmada M, Pitlick W, Carter G, Abern S. Phenobarbital and phenytoin in neonatal seizures: metabolism and tissue distribution. Neurology. 1981;31(9):1107–12.

    Article  CAS  PubMed  Google Scholar 

  114. Tokola RA, Neuvonen PJ. Pharmacokinetics of antiepileptic drugs. Acta Neurol Scand Suppl. 1983;97:17–27.

    Article  CAS  PubMed  Google Scholar 

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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Marsot, A., Boulamery, A., Bruguerolle, B. et al. Population Pharmacokinetic Analysis during the First 2 Years of Life. Clin Pharmacokinet 51, 787–798 (2012). https://doi.org/10.1007/s40262-012-0015-8

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