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Review

Drug metabolism in early infancy: opioids as an illustration

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Pages 287-301 | Received 23 Nov 2017, Accepted 22 Jan 2018, Published online: 30 Jan 2018

References

  • Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology — drug disposition, action, and therapy in infants and children. New England J Med. 2003;349(12):1157–1167.
  • Allegaert K, van de Velde M, van den Anker J. Neonatal clinical pharmacology. Pediatr Anesth. 2014;24(1):30–38.
  • Samardzic J, Turner MA, Bax R, et al. Neonatal medicines research: challenges and opportunities. Expert Opin Drug Metab Toxicol. 2015;11(7):1041–1052.
  • de Wildt SN. Profound changes in drug metabolism enzymes and possible effects on drug therapy in neonates and children. Expert Opin Drug Metab Toxicol. 2011;7(8):935–948.
  • Ince I, Knibbe CA, Danhof M, et al. Developmental changes in the expression and function of cytochrome P450 3A isoforms: evidence from in vitro and in vivo investigations. Clin Pharmacokinet. 2013;52(5):333–345.
  • Strougo A, Yassen A, Monnereau C, et al. Predicting the “First dose in children” of CYP3A-metabolized drugs: evaluation of scaling approaches and insights into the CYP3A7-CYP3A4 switch at young ages. J Clin Pharmacol. 2014;54(9):1006–1015.
  • Lawson JR. Letter to the editor. Birth. 1986;13(2):124–125.
  • Rovner S, Rovner Y. Surgery without anesthesia: can preemies feel pain?. The Washington Post. August 13, 1986;7–8.
  • American Academy of Pediatrics. Neonatal anesthesia. In: Pediatrics. 1987. p. 446.
  • Anand KJ, Hall RW, Desai N, et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. The Lancet. 2004;363(9422):1673–1682.
  • Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. The Lancet. 1987;329(8524):62–66.
  • Merskey H. Pain terms: a list with definitions and notes on usage. Recommended by the IASP subcommittee on taxonomy. Pain. 1979;6:249–252.
  • American Academy of Pediatrics. Committee on Fetus and Newborn. Committee on Drugs. Section on Anesthesiology. Section on Surgery. Canadian Paediatric Society. Fetus and Newborn Committee. Prevention and management of pain and stress in the neonate. Pediatr. 2000;105(2):454–461.
  • Abu-Saad HH, Bours GJ, Stevens B, et al. Assessment of pain in the neonate. Semin Perinatol. 1998;22(5):402–416.
  • Baarslag MA, Allegaert K, van den Anker JN, et al. Paracetamol and morphine for infant and neonatal pain; still a long way to go? Expert Rev Clin Pharmacol. 2017;10(1):111–126.
  • van Dijk M, de Boer JB, Koot HM, et al. The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants. Pain®. 2000;84(2):367–377.
  • Hartley C, Duff EP, Green G, et al. Nociceptive brain activity as a measure of analgesic efficacy in infants. Sci Transl Med. 2017;9:388.
  • de Wildt SN, Kearns GL, Leeder JS, et al. Cytochrome P450 3A. Clin Pharmacokinet. 1999;37(6):485–505.
  • Hines R. Developmental expression of drug metabolizing enzymes: impact on disposition in neonates and young children. Int J Pharm. 2013;452(1):3–7.
  • Krekels E, Danhof M, Tibboel D, et al. Ontogeny of hepatic glucuronidation; Methods and results. Curr Drug Metab. 2012;13(6):728–743.
  • Johnson TN, Tucker GT, Rostami-Hodjegan A. Development of CYP2D6 and CYP3A4 in the first year of life. Clin Pharmacol Ther. 2008;83(5):670–671.
  • Alcorn J, McNamara PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants part I. Clin Pharmacokinet. 2002;41(12):959–998.
  • Allegaert K, Simons SH, Tibboel D, et al. Non-maturational covariates for dynamic systems pharmacology models in neonates, infants, and children: filling the gaps beyond developmental pharmacology. Eur J Pharm Sci. 2017;109:S27–S31.
  • Özdemir M, Crewe KH, Tucker GT, et al. Assessment of in vivo CYP2D6 ACTIVITY: DIFFERENTIAL SENSITIVITY OF COMMONLY USED PROBES TO URINe pH. J Clin Pharmacol. 2004;44(12):1398–1404.
  • Leeder JS, Kearns GL. Interpreting pharmacogenetic data in the developing neonate: the challenge of hitting a moving target. Clin Pharmacol Ther. 2012;92(4):434–436.
  • Allegaert K, van den Anker J. Neonatal drug therapy: the first frontier of therapeutics for children. Clin Pharmacol Ther. 2015;98(3):288–297.
  • Vet NJ, De Hoog M, Tibboel D, et al. The effect of inflammation on drug metabolism: a focus on pediatrics. Drug Discov Today. 2011;16(9):435–442.
  • Wildschut ED, Ahsman MJ, Houmes RJ, et al. Pharmacotherapy in neonatal and pediatric Extracorporeal Membrane Oxygenation (ECMO). Curr Drug Metab. 2012;13(6):767–777.
  • van den Anker JN, van der Heijden BJ, Hop WC, et al. The effect of asphyxia on the pharmacokinetics of ceftazidime in the term newborn. Pediatr Res. 1995;38(5):808–811.
  • Cristea S, Smits A, Kulo A, et al. Amikacin pharmacokinetics to optimize dosing in neonates with perinatal asphyxia treated with hypothermia. Antimicrob Agents Chemother. 2017 Nov 22;61(12). pii: e01282-17.
  • van Overmeire B, Smets K, Lecoutere D, et al. A Comparison of Ibuprofen and Indomethacin for Closure of Patent Ductus Arteriosus. New England J Med. 2000;343(10):674–681.
  • Finta C, Zaphiropoulos PG. The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons. Gene. 2000;260(1–2):13–23.
  • Guengerich FP. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol. 1999;39(1):1–17.
  • Kuip EJ, Zandvliet ML, Koolen SL, et al. A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients. Br J Clin Pharmacol. 2017;83(2):294–313.
  • Muraoka W, Nishizawa D, Fukuda K, et al. Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery. Mol Pain. 2016;12:1–12.
  • Edginton AN, Schmitt W, Voith B, et al. A mechanistic approach for the scaling of clearance in children. Clin Pharmacokinet. 2006;45(7):683–704.
  • Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet. 2006;45(9):931–956.
  • Björkman S. Prediction of cytochrome P450-mediated hepatic drug clearance in neonates, infants and children. Clin Pharmacokinet. 2006;45(1):1–11.
  • Lu H, Rosenbaum S. Developmental pharmacokinetics in pediatric populations. J Pediatr Pharmacol Ther. 2014;19(4):262–276.
  • Alcorn J, McNamara PJ. Ontogeny of hepatic and renal systemic clearance pathways in infants: part II. Clin Pharmacokinet. 2002;41(13):1077–1094.
  • Komori M, Nishio K, Ohi H, et al. Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cytochrome P-450. J Biochemistry. 1989;105(2):161–163.
  • Daly AK. Significance of the Minor Cytochrome P450 3A Isoforms. Clin Pharmacokinet. 2006;45(1):13–31.
  • Kearns GL, Robinson PK, Wilson JT, et al. Cisapride disposition in neonates and infants: in vivo reflection of cytochrome P450 3A4 ontogeny. Clin Pharmacol Ther. 2003;74(4):312–325.
  • Mukherjee KK, Singh SK, Khosla VK, et al. Safety and efficacy of sildenafil citrate in reversal of cerebral vasospasm: A feasibility study. Surg Neurol Int. 2012;3:3.
  • Allegaert K, van Schaik RH, Vermeersch S, et al. Postmenstrual age and CYP2D6 polymorphisms determine tramadol O-demethylation in critically ill neonates and infants. Pediatr Res. 2008;63(6):674–679.
  • Fanni D, Ambu R, Gerosa C, et al. Cytochrome P450 genetic polymorphism in neonatal drug metabolism: role and practical consequences towards a new drug culture in neonatology. Int J Immunopathol Pharmacol. 2014;27(1):5–13.
  • Ingelman-Sundberg M, Rodriguez-Antona C. Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy. Philosophical Trans Royal Soc B: Biol Sci. 2005;360(1460):1563–1570.
  • Burk O, Tegude H, Koch I, et al. Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine. J Biol Chem. 2002;277(27):24280–24288.
  • Brussee JM, Vet NJ, Krekels EH, et al. Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children, and adults with inflammation and organ failure. Br J Clin Pharmacol. 2018;84(2):358–368.
  • Ahsman MJ, Hanekamp M, Wildschut ED, et al. Population pharmacokinetics of midazolam and its metabolites during venoarterial extracorporeal membrane oxygenation in neonates. Clin Pharmacokinet. 2010;49(6):407–419.
  • Simons SH, Anand KJ. Pain control: opioid dosing, population kinetics and side-effects. Semin Fetal Med. 2006;11(4):260–267.
  • Saarenmaa E, Neuvonen PJ, Rosenberg P, et al. Morphine clearance and effects in newborn infants in relation to gestational age. Clin Pharmacol Ther. 2000;68(2):160–166.
  • Kart T, Christrup L, Rasmussen M. Recommended use of morphine in neonates, infants and children based on a literature review: part 1—Pharmacokinetics. Pediatr Anesth. 1997;7(1):5–11.
  • Klimas R, Mikus G. Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: a quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide. Br J Anaesth. 2014;113(6):935–944.
  • Sverrisdóttir E, Lund TM, Olesen AE, et al. A review of morphine and morphine-6-glucuronide’s pharmacokinetic–pharmacodynamic relationships in experimental and clinical pain. Eur J Pharm Sci. 2015;74(SupplementC):45–62.
  • Mercadante S. The role of morphine glucuronides in cancer pain. Palliat Med. 1999;13(2):95–104.
  • Krekels EH, Tibboel D, De Wildt SN, et al. Evidence-based morphine dosing for postoperative neonates and infants. Clin Pharmacokinet. 2014;53(6):553–563.
  • 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):1589–1597.
  • Matic M, Simons SH, van Lingen RA, et al. Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics. 2014;15(10):1287–1295.
  • Anderson BJ, Palmer GM. Recent developments in the pharmacological management of pain in children. Curr Opin Anesthesiology. 2006;19(3):285–292.
  • Lynn A, Nespeca MK, Bratton SL, et al. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analgesia. 1998;86(5):958–963.
  • 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.
  • Róka A, Melinda KT, Vásárhelyi B, et al. Elevated morphine concentrations in neonates treated with morphine and prolonged hypothermia for hypoxic ischemic encephalopathy. Pediatr. 2008;121(4):e844–e849.
  • Byon W, Smith M, Chan P, et al. Establishing best practices and guidance in population modeling: an experience with an internal population pharmacokinetic analysis guidance. CPT: Pharma Sys Pharmacol. 2013;2(7):1–8.
  • Krekels EH, van Hasselt JG, Tibboel D, et al. Systematic evaluation of the descriptive and predictive performance of paediatric morphine population models. Pharm Res. 2011;28(4):797–811.
  • Wang J, Edginton AN, Avant D, et al. Predicting neonatal pharmacokinetics from prior data using population pharmacokinetic modeling. J Clin Pharmacol. 2015;55(10):1175–1183.
  • Krekels EH, van Ham S, Allegaert K, et al. Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants. Eur J Clin Pharmacol. 2015;71(9):1075–1082.
  • Santeiro ML, Christie J, Stromquist C, et al. Pharmacokinetics of continuous infusion fentanyl in newborns. J Perinatology. 1996;17(2):135–139.
  • Gauntlett Ian S, Fisher Dennis M, Hertzka Robert E, et al. Pharmacokinetics of fentanyl in neonatal humans and lambs effects of age. Anesthesiology. 1988;69(5):683–687.
  • Johnson KL, Erickson JP, Holley FO, et al. Fentanyl pharmacokinetics in the pediatric population. Anesthesiology. 1984;61(3):441.
  • Koehntop DE, Rodman JH, Brundage DM, et al. Pharmacokinetics of fentanyl in neonates. Anesth Analgesia. 1986;65(3):227–232.
  • van Driest SL, Marshall MD, Hachey B, et al. Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery. Br J Clin Pharmacol. 2016;81(6):1165–1174.
  • Koren G, Goresky G, Crean P, et al. Pediatric fentanyl dosing based on pharmacokinetics during cardiac surgery. Anesth Analgesia. 1984;63(6):577–582.
  • Ziesenitz VC, Vaughns JD, Koch G, et al. Pharmacokinetics of fentanyl and its derivatives in children: a comprehensive review. Clin Pharmacokinet. 2018;57(2):125–149.
  • Vet NJ, de Hoog M, Tibboel D, et al. The effect of critical illness and inflammation on midazolam therapy in children. Pediatr Crit Care Med. 2012;13(1):e48–e50.
  • Liu T, Lewis T, Gauda E, et al. Mechanistic population pharmacokinetics of morphine in neonates with abstinence syndrome after oral administration of diluted tincture of opium. J Clin Pharmacol. 2016;56(8):1009–1018.
  • Knøsgaard KR, Foster DJ, Kreilgaard M, et al. Pharmacokinetic models of morphine and its metabolites in neonates: systematic comparisons of models from the literature, and development of a new meta-model. Eur J Pharm Sci. 2016;92(SupplementC):117–130.
  • Anand KJ, Anderson BJ, Holford NH, et al. Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial. Br J Anaesth. 2008;101(5):680–689.
  • Hunt A, Joel S, Dick G, et al. Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. J Pediatr. 1999;135(1):47–55.
  • Sadhasivam S, Krekels EH, Chidambaran V, et al. Morphine clearance in children: does race or genetics matter? J Opioid Manag. 2012;8(4):217–226.
  • de Mendizabal NV, Jimenez-Mendez R, Cooke E, et al. A compartmental analysis for morphine and its metabolites in young children after a single oral dose. Clin Pharmacokinet. 2015;54(10):1083–1090.
  • Valkenburg AJ, Calvier EA, van Dijk M, et al. Pharmacodynamics and pharmacokinetics of morphine after cardiac surgery in children with and without down syndrome. Pediatr Crit Care Med. 2016;17(10):930–938.
  • Bouwmeester NJ, Anderson BJ, Tibboel D, et al. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. Br J Anaesth. 2004;92(2):208–217.
  • Peters JW, Anderson BJ, Simons SH, et al. Morphine metabolite pharmacokinetics during venoarterial extra corporeal membrane oxygenation in neonates. Clin Pharmacokinet. 2006;45(7):705–714.
  • Knibbe CA, Krekels EH, van den Anker JN, et al. Morphine glucuronidation in preterm neonates, infants and children younger than 3 years. Clin Pharmacokinet. 2009;48(6):371–385.
  • Wang C, Sadhavisvam S, Krekels EH, et al. Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model. Clin Drug Investig. 2013;33(7):523–534.
  • Elkomy MH, Drover DR, Galinkin JL, et al. Pharmacodynamic analysis of morphine time-to-remedication events in infants and young children after congenital heart surgery. Clin Pharmacokinet. 2016;55(10):1217–1226.
  • Krekels EH, Johnson TN, den Hoedt SM, et al. From pediatric covariate model to semiphysiological function for maturation: part II—sensitivity to physiological and physicochemical properties. CPT: Pharmacometrics Syst Pharmacol. 2012;1(10):1–8.
  • Anderson BJ, Holford NH. Mechanistic basis of using body size and maturation to predict clearance in humans. Drug Metab Pharmacokinet. 2009;24(1):25–36.
  • Elkomy MH, Drover DR, Glotzbach KL, et al. Pharmacokinetics of morphine and its metabolites in infants and young children after congenital heart surgery. Aaps J. 2016;18(1):124–133.
  • Ward RM, Benjamin D, Barrett JS, et al. Safety, dosing, and pharmaceutical quality for studies that evaluate medicinal products (including biological products) in neonates. Pediatr Res. 2017;81(5):692–711.
  • Krekels EH, van Hasselt JG, van den Anker JN, et al. Evidence-based drug treatment for special patient populations through model-based approaches. Eur J Pharm Sci. 2017;109S:S22–S26.
  • Holford NH, Anderson BJ. Why standards are useful for predicting doses. Br J Clin Pharmacol. 2017;83(4):685–687.
  • DDMoRe, sharing knowledge to improve drug development [cited Jan 27, 2018]. Available from: http://www.ddmore.eu/
  • de Cock RF, Allegaert K, Sherwin CM, et al. A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates. Pharm Res. 2014;31(3):754–767.
  • Johnson TN, Rostami-Hodjegan A. Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: parallel shift in incorporating the knowledge of biological elements and increased applicability to drug development and clinical practice. Pediatr Anesth. 2011;21(3):291–301.
  • Pokorna P, Wildschut ED, Vobruba V, et al. The impact of hypothermia on the pharmacokinetics of drugs used in neonates and young infants. Curr Pharm Des. 2015;21(39):5705–5724.
  • de Haan TR, Bijleveld YA, van der Lee JH, et al. Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The pharmacool multicenter study. BMC Pediatr. 2012;12(1):45.
  • de Cock RF, Piana C, Krekels EH, et al. The role of population PK–PD modelling in paediatric clinical research. Eur J Clin Pharmacol. 2011;67(Suppl 1):5–16.
  • Krekels EH, Neely M, Panoilia E, et al. From pediatric covariate model to semiphysiological function for maturation: part I–extrapolation of a covariate model from morphine to zidovudine. CPT: Pharmacometrics Syst Pharmacol. 2012;1(10):e9.
  • Claassen K, Thelen K, Coboeken K, et al. Development of a physiologically-based pharmacokinetic model for preterm neonates: evaluation with in vivo data. Curr Pharm Des. 2015;21(39):5688–5698.
  • Abduljalil K, Jamei M, Rostami-Hodjegan A, et al. Changes in individual drug-independent system parameters during virtual paediatric pharmacokinetic trials: introducing time-varying physiology into a paediatric PBPK model. Aaps J. 2014;16(3):568–576.
  • Jin J. Risks of codeine and tramadol in children. Jama. 2017;318(15):1514.
  • Goulooze SC, Krekels EH, van Dijk M, et al. Towards personalized treatment of pain using a quantitative systems pharmacology approach. Eur J Pharm Sci. 2017 Nov 15;109S:S32-S38.

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