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Handling of Drugs in Children with Abnormal Renal Function

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Pediatric Nephrology

Abstract

Determining the dosage and frequency of a particular drug in a child with kidney dysfunction can often seem daunting. Many therapies have not been fully tested in children, even in those children with normal kidney function. Despite laws instituted in the past two decades to encourage pharmacological studies in pediatric populations, drug dosing in children is often based on extrapolation from adult data. Yet, children often metabolize drugs differently than adults, depending on the drug category or age group. In addition, renal dysfunction adds a further level of complexity to drug dosing as absorption, distribution, metabolism, and secretion of agents can be altered as kidney function worsens. The extent to which derangements in drug handling alter dosage can depend on the GFR, the child’s age or size, the precision of the GFR estimation, or, when in renal failure, the modality of the renal replacement therapy.

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References

  1. Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 1999;80(2):F142–F144.

    Article  PubMed  CAS  Google Scholar 

  2. Conroy S, McIntyre J, Choonara I, Stephenson T. Drug trials in children: problems and the way forward. Br J Clin Pharmacol 2000;49(2):93–97.

    Article  PubMed  CAS  Google Scholar 

  3. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology – drug disposition, action, and therapy in infants and children. N Engl J Med 2003;349(12):1157–1167.

    Article  PubMed  CAS  Google Scholar 

  4. Kearns GL, Spaulding-Barclay M. Adolescent pharmacology: a pertinent issue of medicine as opposed to medicines. Clin Pharmacol Ther 2008;84(6):639–644.

    Article  PubMed  CAS  Google Scholar 

  5. Bartelink IH, Rademaker CM, Schobben AF, Anker JN. van den Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet 2006;45(11):1077–1097.

    Article  PubMed  CAS  Google Scholar 

  6. Daschner M. Drug dosage in children with reduced renal function. Pediatr Nephrol 2005;20(12):1675–1686.

    Article  PubMed  Google Scholar 

  7. Kanneh A. Paediatric pharmacological principles: an update. Part 1: Drug development and pharmacodynamics. Paediatr Nurs 2002;14(8):36–42.

    PubMed  Google Scholar 

  8. Kanneh A. Paediatric pharmacological principles: an update. Part 2. Pharmacokinetics: absorption and distribution. Paediatr Nurs 2002;14(9):39–43.

    Google Scholar 

  9. Conroy S. Paediatric Pharmacy-drug therapy. Hospital Pharmacy 2003;10:49–57.

    Google Scholar 

  10. Dasgupta A. Clinical utility of free drug monitoring. Clin Chem Lab Med 2002;40(10):986–993.

    Article  PubMed  CAS  Google Scholar 

  11. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin Pharmacokinet 2007;46(1):13–58.

    Article  PubMed  CAS  Google Scholar 

  12. Meier-Kriesche HU, Shaw LM, Korecka M, Kaplan B. Pharmacokinetics of mycophenolic acid in renal insufficiency. Ther Drug Monit 2000;22(1):27–30.

    Article  PubMed  CAS  Google Scholar 

  13. Kanneh A. Paediatric pharmacological principles: an update. Part 3. Pharmacokinetics: metabolism and excretion. Paediatr Nurs 2002;14(10):39–43.

    Google Scholar 

  14. Luedtke SA, Kuhn RJ, McCaffrey FM. Pharmacologic management of supraventricular tachycardias in children. Part 2: Atrial flutter, atrial fibrillation, and junctional and atrial ectopic tachycardia. Ann Pharmacother 1997;31(11):1347–1359.

    PubMed  CAS  Google Scholar 

  15. Luedtke SA, Kuhn RJ, McCaffrey FM. Pharmacologic management of supraventricular tachycardias in children. Part 1: Wolff-Parkinson-White and atrioventricular nodal reentry. Ann Pharmacother 1997;31(10):1227–1243.

    PubMed  CAS  Google Scholar 

  16. Rushmore TH, Kong AN. Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Curr Drug Metab 2002;3(5):481–490.

    Article  PubMed  CAS  Google Scholar 

  17. Korashy HM, Elbekai RH, El Kadi AO. Effects of renal diseases on the regulation and expression of renal and hepatic drug-metabolizing enzymes: a review. Xenobiotica 2004;34(1):1–29.

    Article  PubMed  CAS  Google Scholar 

  18. Kato R. Drug metabolism under pathological and abnormal physiological states in animals and man. Xenobiotica 1977;7(1–2):25–92.

    Article  PubMed  CAS  Google Scholar 

  19. Kennedy M. Hormonal regulation of hepatic drug-metabolizing enzyme activity during adolescence. Clin Pharmacol Ther 2008;84(6):662–673.

    Article  PubMed  CAS  Google Scholar 

  20. Milavetz G, Vaughan LM, Weinberger MM, Hendeles L. Evaluation of a scheme for establishing and maintaining dosage of theophylline in ambulatory patients with chronic asthma. J Pediatr 1986;109(2):351–354.

    Article  PubMed  CAS  Google Scholar 

  21. Jain AB, Fung JJ, Tzakis AG, Venkataramanan R, Abu-Elmagd K, Alessiani M et al. Comparative study of cyclosporine and FK 506 dosage requirements in adult and pediatric orthotopic liver transplant patients. Transplant Proc 1991;23(6):2763–2766.

    PubMed  CAS  Google Scholar 

  22. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 2007;76(3):391–396.

    PubMed  Google Scholar 

  23. Somogyi A. Renal transport of drugs: specificity and molecular mechanisms. Clin Exp Pharmacol Physiol 1996;23(10–11):986–989.

    Article  PubMed  CAS  Google Scholar 

  24. Veltri MA, Neu AM, Fivush BA, Parekh RS, Furth SL. Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: Special considerations in pediatric patients. Paediatr Drugs 2004;6:45–65.

    Article  PubMed  Google Scholar 

  25. Pea F, Viale P, Pavan F, Furlanut M. Pharmacokinetic considerations for antimicrobial therapy in patients receiving renal replacement therapy. Clin Pharmacokinet 2007;46:997–1038.

    Article  PubMed  CAS  Google Scholar 

  26. Olyaei AL, De Mattos AM, Bennett WM. Prescribing drugs in renal disease. In Brenner & Rector’s the Kidney, 6th edn. Brenner BM (ed.). Philadelphia, PA, W. B. Saunders Company, 2000, pp. 2606–2651.

    Google Scholar 

  27. Keller F, Wilms H, Schultze G, Offerman G, Molzahn M. Effect of plasma protein binding, volume of distribution and molecular weight on the fraction of drugs eliminated by hemodialysis. Clin Nephrol 1983;19:201–205.

    PubMed  CAS  Google Scholar 

  28. Hecking E, Bragg-Gresham JL, Rayner HC, Pisoni RL, Andreucci VE, Combe C, Greenwood R, McCullough K, Feldman HI, Young EW, Held PJ, Port FK. Haemodialysis prescription, adherence and nutritional indicators in five European countries: Results from the dialysis outcomes and practice patterns study (DOPPS). Nephrol Dial Transplant 2004;19:100–107.

    Article  PubMed  Google Scholar 

  29. Centers for Disease Control, Division of Healthcare Quality Promotion [online]: http://www.cdc.gov/ncidod/dhqp/pdf/dialysis/dialysis99.pdf, 1999.

  30. DeSoi CA, Sahm DF, Umans JG. Vancomycin elimination during high-flux hemodialysis: Kinetic model and comparison of four membranes. Am J Kidney Dis 1992;20:354–360.

    PubMed  CAS  Google Scholar 

  31. Aronoff GR, Berns JS, Brier ME, Golper TA, Morrison G, Singer I, Swan SK, Bennett WM. Drug Prescribing in Renal Failure, 4th edn. Philadelphia, PA, American College of Physicians, 1999.

    Google Scholar 

  32. Kober A, Sjoholm I, Borga O, Odar-Cederlof I. Protein binding of diazepam and digitoxin in uremic and normal serum. Biochem Pharmacol 1979;28:1037–1042.

    Article  PubMed  CAS  Google Scholar 

  33. Golper TA, Pulliam J, Bennett WM. Removal of therapeutic drugs by continuous arteriovenous hemofiltration. Arch Intern Med 1985;145:1651–1652.

    Article  PubMed  CAS  Google Scholar 

  34. Reidenberg MM, Drayer DE. Drug therapy in renal failure. Annu Rev Pharmacol Toxicol 1980;20:45–54.

    Article  PubMed  CAS  Google Scholar 

  35. Golper TA, Bennett WM. Drug removal by continuous arteriovenous haemofiltration. A review of the evidence in poisoned patients. Med Toxicol Adverse Drug Exp 1988;3:341–349.

    Article  PubMed  CAS  Google Scholar 

  36. Bohler J, Donauer J, Keller F. Pharmacokinetic principles during continuous renal replacement therapy: Drugs and dosage. Kidney Int 1999;56(suppl 72):S24–S28.

    Google Scholar 

  37. Pollard TA, Lampasona V, Akkerman S, Tom K, Hooks MA, Mullins RE, Maroni BJ. Vancomycin redistribution: Dosing recommendations following high-flux hemodialysis. Kidney Int 1994;45:232–237.

    Article  PubMed  CAS  Google Scholar 

  38. Welage LS, Mason NA, Hoffman EJ, Odeh RM, Dombrouski J, Patel JA, Swartz RD. Influence of cellulose triacetate hemodialyzers on vancomycin pharmacokinetics. J Am Soc Nephrol 1995;6:1284–1290.

    PubMed  CAS  Google Scholar 

  39. Reetze-Bonorden P, Bohler J, Keller E. Drug dosage in patients during continuous renal replacement therapy. pharmacokinetic and therapeutic considerations. Clin Pharmacokinet 1993;24:362–379.

    Article  PubMed  CAS  Google Scholar 

  40. Joy MS, Matzke GR, Armstrong DK, Marx MA, Zarowitz BJ. A primer on continuous renal replacement therapy for critically ill patients. Ann Pharmacother 1998;32:362–375.

    Article  PubMed  CAS  Google Scholar 

  41. Golper TA. Drug removal during continuous hemofiltration or hemodialysis. Contrib Nephrol 1991;93:110–116.

    PubMed  CAS  Google Scholar 

  42. Lindsay CA, Bawdon R, Quigley R. Clearance of ticarcillin-clavulanic acid by continuous venovenous hemofiltration in three critically ill children, two with and one without concomitant extracorporeal membrane oxygenation. Pharmacotherapy 1996;16:458–462.

    PubMed  CAS  Google Scholar 

  43. Fischbach M, Edefonti A, Schroder C, Watson A. The European Pediatric Dialysis Working Group: Hemodialysis in children: General practical guidelines. Pediatr Nephrol 2005;20:1054–1066.

    Article  PubMed  CAS  Google Scholar 

  44. Agarwal R, Toto RD. Gentamicin clearance during hemodialysis: A comparison of high-efficiency cuprammonium rayon and conventional cellulose ester hemodialyzers. Am J Kidney Dis 1993;22:296–299.

    PubMed  CAS  Google Scholar 

  45. Amin NB, Padhi ID, Touchette MA, Patel RV, Dunfee TP, Anandan JV. Characterization of gentamicin pharmacokinetics in patients hemodialyzed with high-flux polysulfone membranes. Am J Kidney Dis 1999;34:222–227.

    Article  PubMed  CAS  Google Scholar 

  46. Rumpf KW, Rieger J, Ansorg R, Doht B, Scheler F. Binding of antibiotics by dialysis membranes and its clinical relevance. Proc Eur Dial Transplant Assoc 1977;14:607–609.

    PubMed  CAS  Google Scholar 

  47. Bouman CS, van Kan HJ, Koopmans RP, Korevaar JC, Schultz MJ, Vroom MB. Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing. Intensive Care Med 2006;32:2013–2019.

    Article  PubMed  Google Scholar 

  48. Reetze-Bonorden P, Böhler J, Keller E. Drug dosage in patients during continous renal replacement therapy. Pharmacokinetic and therapeutic considerations. Clin Pharmacokinet 1993;24:362–379.

    Google Scholar 

  49. Golper TA, Wedel SK, Kaplan AA, Saad AM, Donta ST, Paganini EP. Drug removal during continuous arteriovenous hemofiltration: Theory and clinical observations. Int J Artif Organs 1985;8:307–312.

    PubMed  CAS  Google Scholar 

  50. Ronco C, Brendolan A, Bragantini L, Fabris A, Feriani M, Chiaramonte S, Dell’Aquila R, Milan M, La Greca G. Solute and water transport during continuous arteriovenous hemofiltration (CAVH). Int J Artif Organs 1987;10:179–184.

    PubMed  CAS  Google Scholar 

  51. Matzke GR, O’Connell MB, Collins AJ, Keshaviah PR. Disposition of vancomycin during hemofiltration. Clin Pharmacol Ther 1986;40:425–430.

    Article  PubMed  CAS  Google Scholar 

  52. Golper TA. Update on drug sieving coefficients and dosing adjustments during continuous renal replacement therapies. Contrib Nephrol 2001;(132):349–353.

    Google Scholar 

  53. Uchino S, Cole L, Morimatsu H, Goldsmith D, Bellomo R. Clearance of vancomycin during high-volume haemofiltration: Impact of pre-dilution. Intensive Care Med 2002;28:1664–1667.

    Article  PubMed  Google Scholar 

  54. Isla A, Maynar J, Sanchez-Izquierdo JA, Gascon AR, Arzuaga A, Corral E, Pedraz JL. Meropenem and continuous renal replacement therapy: In vitro permeability of 2 continuous renal replacement therapy membranes and influence of patient renal function on the pharmacokinetics in critically ill patients. J Clin Pharmacol 2005;45:1294–1304.

    Article  PubMed  CAS  Google Scholar 

  55. Maher JF, Maher AT. Continuous ambulatory peritoneal dialysis. Am Fam Physician 1989;40:187–192.

    PubMed  CAS  Google Scholar 

  56. Manley HJ, Bailie GR, Frye RF, McGoldrick MD. Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients. Perit Dial Int 2001;21:378–385.

    PubMed  CAS  Google Scholar 

  57. Porto I, John EG, Heilliczer J. Removal of phenobarbital during continuous cycling peritoneal dialysis in a child. Pharmacotherapy 1997;17:832–835.

    PubMed  CAS  Google Scholar 

  58. Warady BA, Schaefer F, Holloway M, Alexander S, Kandert M, Piraino B, Salusky I, Tranaeus A, Divino J, Honda M, Mujais S, Verrina E. International society for peritoneal dialysis (ISPD) advisory committee on peritonitis management in pediatric patients: Consensus guidelines for the treatment of peritonitis in pediatric patients receiving peritoneal dialysis. Perit Dial Int 2000;20:610–624.

    PubMed  CAS  Google Scholar 

  59. Warady BA, Feneberg R, Verrina E, Flynn JT, Muller-Wiefel DE, Besbas N, Zurowska A, Aksu N, Fischbach M, Sojo E, Donmez O, Sever L, Sirin A, Alexander SR, Schaefer F. IPPR: Peritonitis in children who receive long-term peritoneal dialysis: A prospective evaluation of therapeutic guidelines. J Am Soc Nephrol 2007;18:2172–2179.

    Article  PubMed  Google Scholar 

  60. Blowey DL, Warady BA, Abdel-Rahman S, Frye RF, Manley HJ. Vancomycin disposition following intraperitoneal administration in children receiving peritoneal dialysis. Perit Dial Int 2007;27:79–85.

    PubMed  CAS  Google Scholar 

  61. Paulson MF, Welling PG. Calculation of serum digoxin levels in patients with normal and impaired renal function. J Clin Pharmacol 1976;16(11/12):660–665.

    PubMed  CAS  Google Scholar 

  62. Laskin OL, Longstreth JA, Whelton A et al. Effect of renal failure on the pharmacokinetics of acyclovir. Am J Med 1982;73(1A):197–201.

    Article  PubMed  CAS  Google Scholar 

  63. Shevchuk YM, Taylor DM. Aminoglycoside Volume of Distribution in Pediatric Patients. DICP 1990;24(3):273–276.

    PubMed  CAS  Google Scholar 

  64. Liu H, Delgado MR. Influence of sex, age, weight, and carbamazepine dose on serum concentrations, concentration rations, and level/dose ratios of carbamazepine and its metabolites. Ther Drug Monit 1994;16(5):469–476.

    Article  PubMed  CAS  Google Scholar 

  65. Kamel Mohamed OH, Wahba IM, Watnick S, Earle SB, Bennett WM, Ayres JW, Munar MY. Administration of tobramycin in the beginning of the hemodialysis session: A novel intradialytic dosing regimen. Clin J Am Soc Nephrol 2007;2:694–699.

    Article  PubMed  Google Scholar 

  66. Warady BA, Bunchman T. Dialysis therapy for children with acute renal failure: Survey results. Pediatr Nephrol 2000;15:11–13.

    Article  PubMed  CAS  Google Scholar 

  67. Symons JM, Chua AN, Somers MJ, Baum MA, Bunchman TE, Benfield MR, Brophy PD, Blowey D, Fortenberry JD, Chand D, Flores FX, Hackbarth R, Alexander SR, Mahan J, McBryde KD, Goldstein SL. Demographic characteristics of pediatric continuous renal replacement therapy: A report of the prospective pediatric continuous renal replacement therapy registry. Clin J Am Soc Nephrol 2007;2:732–738.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Samaritan Medical Group, Corvallis, Oregon

    Ihab M. Wahba

  2. Division of Nephrology & Hypertension, Oregon Health Sciences University, Portland, OR, USA

    Ali J. Olyaei

  3. Division of Nephrology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, USA

    David Rozansky

  4. Norwest Renal Clinic, Legacy Good Samaritan Hospital Transplant Services, Portland, OR, USA

    William M. Bennett

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  1. Ihab M. Wahba
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  2. Ali J. Olyaei
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  3. David Rozansky
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  4. William M. Bennett
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Editor information

Editors and Affiliations

  1. Medical College of Wisconsin, Wisconsin, USA

    Ellis Avner (Director, Children's Research Institute, CHHS, Associate Dean for Research, Professor of Pediatrics and Physiology) (Director, Children's Research Institute, CHHS, Associate Dean for Research, Professor of Pediatrics and Physiology)

  2. Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    William Harmon (Professor of Pediatrics, Director, Pediatric Nephrology) (Professor of Pediatrics, Director, Pediatric Nephrology)

  3. Service de Néphrologie Pédiatrique Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Hôpital Necker‐Enfants Malades, 149, rue de Sèvres, 75743, Paris Cedex 15, France

    Patrick Niaudet

  4. Department of Pediatrics Wakayama Medical University, Wakayama Medical University Hospital, 641–8510811–1, Kimiidera, Wakayama City, Japan

    Norishige Yoshikawa (Professor and Chair Pediatrician‐in‐Chief) (Professor and Chair Pediatrician‐in‐Chief)

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Wahba, I.M., Olyaei, A.J., Rozansky, D., Bennett, W.M. (2009). Handling of Drugs in Children with Abnormal Renal Function. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76341-3_69

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  • DOI: https://doi.org/10.1007/978-3-540-76341-3_69

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-76327-7

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