Developmental pharmacokinetics and pharmacodynamics of parenteral opioids and nonsteroidal anti-nflammatory drugs in neonates and infants
Keywords:
Infant, Infant care, Analgesics, Opioid, Pharmacokinetics, Pharmacology
Abstract
Introduction: Pharmacology of infants is understudied and different from other populations.
Objective: To review the unique features of neonatal and infant physiology that impact drug handling and the pharmacokinetics of analgesics, including opioids, ketorolac and acetaminophen.
Materials and methods: This article is a narrative review of the literature from the authors' point of view that constitutes a summary of the information presented at the annual Colombian Society for Anesthesia meeting in Cali, Colombia June 2015.
Conclusions: Pharmacology in neonates and infants is unique and must be considered in this vulnerable population. Recommendations for administration of these analgesics are presented based on their unique pharmacokinetic properties. Individual patient variation and clinical response must also be taken into account.
References
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15. Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiology. 1987;66:136-9.
16. McRorie TI, Lynn AM, Nespeca MK, Opheim KE, Slattery JT. The maturation of morphine clearance and metabolism. Am J Dis Child. 1992;146:972-6.
17. Lynn A, Nespeca MK, Bratton SL, Strauss SG, Shen DD. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analg 1998;86:958-63
18. Krekels EH, Tibboel D, de Wildt SN, Ceelie I, Dahan A, van Dijk M, et al. Evidence-based morphine dosing for postoperative neonates and infants. Clin Pharmacokinet. 2014;53:553-63.
19. Lynn AM, Nespeca MK, Bratton SL, Shen DD. Intravenous morphine in postoperative infants: intermittent bolus dosing versus targeted continuous infusions. Pain. 2000;88: 89-95.
20. 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;92:208-17.
21. Lynn AM, Nespeca MK, Opheim KE, Slattery JT. Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. Anesth Analg. 1993;77:695-701.
22. Ross AK, Davis PJ, deL Dear G, Ginsberg B, McGowan FX, Stiller RD, et al. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg. 2001;93:1393-401.
23. Eck JB, Lynn AM. Use of remifentanil in infants. Paediatr Anaesth. 1998;8:437-9.
24. Davis PJ, Galinkin J, McGowan FX, Lynn AM, Yaster M, Rabb MF, et al. A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles. Anesth Analg. 2001;93:1380-6 [table of contents
25. Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005;100:1599-604.
26. Hume-Smith H, McCormack J, Montgomery C, Brant R, Malherbe S, Mehta D, et al. The effect of age on the dose of remifentanil for tracheal intubation in infants and children. Paediatr Anaesth. 2010;20:19-27.
27. Gupta A, Daggett C, Drant S, Rivero N, Lewis A. Prospective randomized trial of ketorolac after congenital heart surgery. J Cardiothorac Vasc Anesth. 2004;18:454-7.
28. Jett MF, Ramesha CS, Brown CD, Chiu S, Emmett C, Voronin T, et al. Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. J Pharmacol Exp Ther. 1999;288:1288-97.
29. Hamunen K, Maunuksela EL, Sarvela J, Bullingham RE, Olkkola KT. Stereoselective pharmacokinetics of ketorolac in children, adolescents and adults. Acta Anaesthesiol Scand. 1999;43:1041-6.
30. Kauffman RE, Lieh-Lai MW, Uy HG, Aravind MK. Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Clin Pharmacol Ther. 1999;65:382-8.
31. Lynn AM, Bradford H, Kantor ED, Andrew M, Vicini P, Anderson GD. Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months. Paediatr Anaesth. 2011;21:325-34.
32. Anderson BJ, Woollard GA, Holford NH. Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy. Eur J Clin Pharmacol. 2001;57:559-69.
33. Anderson BJ, Pons G, Autret-Leca E, Allegaert K, Boccard E. Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis. Paediatr Anaesth. 2005;15:282-92.
34. Allegaert K, Van der Marel CD, Debeer A, Pluim MA, Van Lingen RA, Vanhole C, et al. Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age. Arch Dis Child Fetal Neonatal Ed. 2004;89:F25-8.
35. Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child. 2011;96:575-80.
36. 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;101:523-30.
37. Ceelie I, de Wildt SN, van Dijk M, van den Berg MM, van den Bosch GE, Duivenvoorden HJ, et al. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial. JAMA. 2013;309:149-54.
2. Greenbaum L. Pathophysiology of body fluids and fluid therapy. In: Behrman R, Kliegman R, Jenson H, editors. Nelson textbook of pediatrics. 17th ed. Philadelphia: Saunders; 2004. p. 267-8.
3. Williams DG, Patel A, Howard RF. Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br J Anaesth. 2002;89:839-45.
4. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med. 2009;361:827-8.
5. Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codein fatalities after tonsillectomy in North American children. Pediatrics. 2012;129:e1343-7.
6. Davis P, Bosenberg A. Pharmacology of pediatric anesthesia. In: Davis P,Cladis F Motoyama E, editors. Smith's anesthesia for infants and children. 8th ed. St. Louis: Mosby; 2011. p.179-263.
7. Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76:334-11.
8. Anderson BJ. Pediatric models for adult target-controlled infusion pumps. Paediatr Anaesth. 2010;20:223-32.
9. Anderson BJ, Hodkinson B. Are there still limitations for the use of target-controlled infusion in children? Curr Opin Anaesthesiol. 2010;23:356-62.
10. Krekels EH, DeJongh J, van Lingen RA, van der Marel CD, Choonara I, Lynn AM, et al. Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children. Clin Pharmacokinet. 2011;50:51-63.
11. Jimenez N, Galinkin JL. Personalizing pediatric pain medicine: using population-speciiic pharmacogenetics, genomics, and other - omics approaches to predict response. Anesth Analg. 2015;121:183-7.
12. Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95:376-82.
13. Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3:229-43.
14. Aklillu E, Persson I, Bertilsson L, Johansson I, Rodrigues F, Ingelman-Sundberg M. Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther. 1996;278:441-6.
15. Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiology. 1987;66:136-9.
16. McRorie TI, Lynn AM, Nespeca MK, Opheim KE, Slattery JT. The maturation of morphine clearance and metabolism. Am J Dis Child. 1992;146:972-6.
17. Lynn A, Nespeca MK, Bratton SL, Strauss SG, Shen DD. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analg 1998;86:958-63
18. Krekels EH, Tibboel D, de Wildt SN, Ceelie I, Dahan A, van Dijk M, et al. Evidence-based morphine dosing for postoperative neonates and infants. Clin Pharmacokinet. 2014;53:553-63.
19. Lynn AM, Nespeca MK, Bratton SL, Shen DD. Intravenous morphine in postoperative infants: intermittent bolus dosing versus targeted continuous infusions. Pain. 2000;88: 89-95.
20. 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;92:208-17.
21. Lynn AM, Nespeca MK, Opheim KE, Slattery JT. Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery. Anesth Analg. 1993;77:695-701.
22. Ross AK, Davis PJ, deL Dear G, Ginsberg B, McGowan FX, Stiller RD, et al. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg. 2001;93:1393-401.
23. Eck JB, Lynn AM. Use of remifentanil in infants. Paediatr Anaesth. 1998;8:437-9.
24. Davis PJ, Galinkin J, McGowan FX, Lynn AM, Yaster M, Rabb MF, et al. A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles. Anesth Analg. 2001;93:1380-6 [table of contents
25. Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005;100:1599-604.
26. Hume-Smith H, McCormack J, Montgomery C, Brant R, Malherbe S, Mehta D, et al. The effect of age on the dose of remifentanil for tracheal intubation in infants and children. Paediatr Anaesth. 2010;20:19-27.
27. Gupta A, Daggett C, Drant S, Rivero N, Lewis A. Prospective randomized trial of ketorolac after congenital heart surgery. J Cardiothorac Vasc Anesth. 2004;18:454-7.
28. Jett MF, Ramesha CS, Brown CD, Chiu S, Emmett C, Voronin T, et al. Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. J Pharmacol Exp Ther. 1999;288:1288-97.
29. Hamunen K, Maunuksela EL, Sarvela J, Bullingham RE, Olkkola KT. Stereoselective pharmacokinetics of ketorolac in children, adolescents and adults. Acta Anaesthesiol Scand. 1999;43:1041-6.
30. Kauffman RE, Lieh-Lai MW, Uy HG, Aravind MK. Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Clin Pharmacol Ther. 1999;65:382-8.
31. Lynn AM, Bradford H, Kantor ED, Andrew M, Vicini P, Anderson GD. Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months. Paediatr Anaesth. 2011;21:325-34.
32. Anderson BJ, Woollard GA, Holford NH. Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy. Eur J Clin Pharmacol. 2001;57:559-69.
33. Anderson BJ, Pons G, Autret-Leca E, Allegaert K, Boccard E. Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis. Paediatr Anaesth. 2005;15:282-92.
34. Allegaert K, Van der Marel CD, Debeer A, Pluim MA, Van Lingen RA, Vanhole C, et al. Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age. Arch Dis Child Fetal Neonatal Ed. 2004;89:F25-8.
35. Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child. 2011;96:575-80.
36. 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;101:523-30.
37. Ceelie I, de Wildt SN, van Dijk M, van den Berg MM, van den Bosch GE, Duivenvoorden HJ, et al. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial. JAMA. 2013;309:149-54.
How to Cite
1.
Martin L, Jiménez N, Lynn AM. Developmental pharmacokinetics and pharmacodynamics of parenteral opioids and nonsteroidal anti-nflammatory drugs in neonates and infants. Colomb. J. Anesthesiol. [Internet]. 2017 Jan. 1 [cited 2024 Apr. 19];45(1):72-9. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/51
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2017-01-01
How to Cite
1.
Martin L, Jiménez N, Lynn AM. Developmental pharmacokinetics and pharmacodynamics of parenteral opioids and nonsteroidal anti-nflammatory drugs in neonates and infants. Colomb. J. Anesthesiol. [Internet]. 2017 Jan. 1 [cited 2024 Apr. 19];45(1):72-9. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/51
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