Impact of nutrition on pharmacokinetics of anti-neoplastic agents

It has been estimated that approximately 80% of the world's pediatric popul ation lives in countries with limited resources, and that 43% of these chil dren are malnourished. In children with cancer, malnutrition may antedate t he diagnosis or be a result of aggressive chemotherapeutic regimens, Studie s have shown that children with cancer and malnutrition have a less favorab le prognosis, a higher risk of early relapse, and tolerate chemotherapy poo rly when compared with children with normal nutritional status. Improvement s in nutritional status may improve tolerance to chemotherapy. An understan ding of the mechanisms responsible for the effects of malnutrition on drug disposition and pharmacodynamic response is important, especially for anti- neoplastic agents, which have a narrow therapeutic index and may be associa ted with potentially severe or life-threatening side-effects. Several facto rs related to malnutrition have been suggested to alter drug disposition. D iminished protein "status" in malnourished children results in lower amount s of plasma proteins, increasing the concentration of free drug available t o exert its cytotoxic effect. Severely malnourished individuals also exhibi t decreased oxidative metabolism and reduced glomerular filtration rate (GF R), potentially increasing concentrations of parent drug or active metaboli tes, Malnourished children receiving chemotherapy for the treatment of an u nderlying malignancy may need specifically "tailored" protocols to achieve therapeutic response while minimizing adverse acute and long-term side effe cts. The role of specific interventions, such as correction of nutritional status or pharmacokinetic drug monitoring, should be evaluated in this cont ext, (C) 1998 Wiley-Liss, Inc.