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Reprinted from Childhood Leukemias with permission from Cambridge University Press; edited by St. Jude pediatric oncologist, Ching-Hon Pui, MD.
Childhood leukemias are among the most drug-responsive of human malignancies. More than 70% of children with acute lymphoblastic leukemia (ALL) can now be cured, largely by systemic chemotherapy.
Pharmacokinetics is the study of the absorption, distribution, metabolism, and excretion of drugs.Pharmacodynamics describes the relationship between pharmacokinetics and pharmacologic effect, either adverse or desired. It is well established that there is substantial interindividual variability in the pharmacokinetics of many antileukemic agents in children.
Interpatient pharmacokinetic variability characterizes the disposition of many drugs. In the case of drugs with a wide therapeutic index ( e.g., penicillins), such variability is unlikely to affect either clinical efficacy or toxicity. In the vast majority of patients, the drugs can be given in high enough doses to assure plasma concentrations that are very likely to produce the desired therapeutic response with little risk of toxicity. With antileukemic drugs, however, there is much less margin for error, due to their very narrow therapeutic index.
Many investigations have established the relationship between administered dosage and plasma (or tissue) concentrations of drugs and metabolites, and in some cases between those concentrations and pharmacologic effect. Interindividual differences in the pharmacokinetics of antileukemic agents can affect the efficacy and toxicity of antileukemic therapy.
Childhood Leukemias is available in the libraries of most medical schools and from major book sellers.
Ching-Hon Pui, M.D.
St. Jude Children's Research Hospital
Publisher: Cambridge University Press