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. 1994 Dec;102(Suppl 11):111–117. doi: 10.1289/ehp.94102s11111

Pharmacokinetics in the child.

W R Crom 1
PMCID: PMC1566750  PMID: 7737035

Abstract

Pharmacokinetic studies have made many significant contributions to rational therapeutics in children. Pharmacokinetic data have helped distinguish between differences in drug disposition and drug sensitivity in children as compared to adults and led to the establishment of age-specific dosage guidelines. Factors influencing the observed differences between drug disposition in children and adults are reviewed. Specific examples utilizing anticancer drugs are presented. The use of model substrates to study hepatic drug metabolism and renal excretion in children is described and some results are discussed. The significance of genetic polymorphic drug metabolism is presented and the use of model substrates to determine individual metabolic phenotypes is described. The use of pharmacokinetic data to define the maximum-tolerated systemic exposure rather than the maximum-tolerated dosage of anticancer drugs in children is presented.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brion L., Fleischman A. R., Schwartz G. J. Evaluation of four length-weight formulas for estimating body surface area in newborn infants. J Pediatr. 1985 Nov;107(5):801–803. doi: 10.1016/s0022-3476(85)80423-6. [DOI] [PubMed] [Google Scholar]
  2. Crom W. R., Glynn-Barnhart A. M., Rodman J. H., Teresi M. E., Kavanagh R. E., Christensen M. L., Relling M. V., Evans W. E. Pharmacokinetics of anticancer drugs in children. Clin Pharmacokinet. 1987 Mar;12(3):168–213. doi: 10.2165/00003088-198712030-00002. [DOI] [PubMed] [Google Scholar]
  3. Crom W. R., Relling M. V., Christensen M. L., Rivera G. K., Evans W. E. Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine. Clin Pharmacol Ther. 1991 Aug;50(2):132–140. doi: 10.1038/clpt.1991.117. [DOI] [PubMed] [Google Scholar]
  4. Crom W. R., Webster S. L., Bobo L., Teresi M. E., Relling M. V., Evans W. E. Simultaneous administration of multiple model substrates to assess hepatic drug clearance. Clin Pharmacol Ther. 1987 Jun;41(6):645–650. doi: 10.1038/clpt.1987.90. [DOI] [PubMed] [Google Scholar]
  5. Evans W. E. Clinical pharmacodynamics of anticancer drugs: a basis for extending the concept of dose-intensity. Blut. 1988 Jun;56(6):241–248. doi: 10.1007/BF00320282. [DOI] [PubMed] [Google Scholar]
  6. Evans W. E., Petros W. P., Relling M. V., Crom W. R., Madden T., Rodman J. H., Sunderland M. Clinical pharmacology of cancer chemotherapy in children. Pediatr Clin North Am. 1989 Oct;36(5):1199–1230. doi: 10.1016/s0031-3955(16)36765-7. [DOI] [PubMed] [Google Scholar]
  7. Evans W. E., Relling M. V. Clinical pharmacokinetics-pharmacodynamics of anticancer drugs. Clin Pharmacokinet. 1989 Jun;16(6):327–336. doi: 10.2165/00003088-198916060-00001. [DOI] [PubMed] [Google Scholar]
  8. Evans W. E., Relling M. V., Petros W. P., Meyer W. H., Mirro J., Jr, Crom W. R. Dextromethorphan and caffeine as probes for simultaneous determination of debrisoquin-oxidation and N-acetylation phenotypes in children. Clin Pharmacol Ther. 1989 May;45(5):568–573. doi: 10.1038/clpt.1989.74. [DOI] [PubMed] [Google Scholar]
  9. Evans W. E., Relling M. V., Rodman J. H., Crom W. R. Anticancer therapy as a pediatric pharmacodynamic paradigm. Dev Pharmacol Ther. 1989;13(2-4):85–95. doi: 10.1159/000457589. [DOI] [PubMed] [Google Scholar]
  10. Evans W. E., Relling M. V., de Graaf S., Rodman J. H., Pieper J. A., Christensen M. L., Crom W. R. Hepatic drug clearance in children: studies with indocyanine green as a model substrate. J Pharm Sci. 1989 Jun;78(6):452–456. doi: 10.1002/jps.2600780605. [DOI] [PubMed] [Google Scholar]
  11. Evans W. E., Rodman J. H., Relling M. V., Crom W. R., Rivera G. K., Pratt C. B., Crist W. M. Concept of maximum tolerated systemic exposure and its application to phase I-II studies of anticancer drugs. Med Pediatr Oncol. 1991;19(3):153–159. doi: 10.1002/mpo.2950190302. [DOI] [PubMed] [Google Scholar]
  12. Galinsky R. E., Chałasinska B. Effect of taurolithocholate on in vivo sulfation and glucuronidation of acetaminophen in rats. Pharm Res. 1988 Jan;5(1):61–64. doi: 10.1023/a:1015871713954. [DOI] [PubMed] [Google Scholar]
  13. Gehan E. A., George S. L. Estimation of human body surface area from height and weight. Cancer Chemother Rep. 1970 Aug;54(4):225–235. [PubMed] [Google Scholar]
  14. Glaubiger D. L., von Hoff D. D., Holcenberg J. S., Kamen B., Pratt C., Ungerleider R. S. The relative tolerance of children and adults to anticancer drugs. Front Radiat Ther Oncol. 1981;16:42–49. doi: 10.1159/000403090. [DOI] [PubMed] [Google Scholar]
  15. Haycock G. B., Schwartz G. J., Wisotsky D. H. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr. 1978 Jul;93(1):62–66. doi: 10.1016/s0022-3476(78)80601-5. [DOI] [PubMed] [Google Scholar]
  16. Kearns G. L., Mallory G. B., Jr, Crom W. R., Evans W. E. Enhanced hepatic drug clearance in patients with cystic fibrosis. J Pediatr. 1990 Dec;117(6):972–979. doi: 10.1016/s0022-3476(05)80149-0. [DOI] [PubMed] [Google Scholar]
  17. Petros W. P., Evans W. E. Pharmacokinetics and pharmacodynamics of anticancer agents: contributions to the therapy of childhood cancer. Pharmacotherapy. 1990;10(5):313–325. [PubMed] [Google Scholar]
  18. Prandota J. Drug disposition in cystic fibrosis: progress in understanding pathophysiology and pharmacokinetics. Pediatr Infect Dis J. 1987 Dec;6(12):1111–1126. [PubMed] [Google Scholar]
  19. Relling M. V., Cherrie J., Schell M. J., Petros W. P., Meyer W. H., Evans W. E. Lower prevalence of the debrisoquin oxidative poor metabolizer phenotype in American black versus white subjects. Clin Pharmacol Ther. 1991 Sep;50(3):308–313. doi: 10.1038/clpt.1991.141. [DOI] [PubMed] [Google Scholar]
  20. Relling M. V. Polymorphic drug metabolism. Clin Pharm. 1989 Dec;8(12):852–863. [PubMed] [Google Scholar]
  21. Rodman J. H., Maneval D. C., Magill H. L., Sunderland M. Measurement of Tc-99m DTPA serum clearance for estimating glomerular filtration rate in children with cancer. Pharmacotherapy. 1993 Jan-Feb;13(1):10–16. [PubMed] [Google Scholar]
  22. Weinberger M. M. Drug clearance in patients with cystic fibrosis. Clin Pharmacol Ther. 1992 Jul;52(1):106–107. doi: 10.1038/clpt.1992.111. [DOI] [PubMed] [Google Scholar]

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