Original ArticlesInterspecies Scaling of Maximum Tolerated Dose of Anticancer Drugs: Relevance to Starting Dose for Phase I Clinical TrialsMahmood, IftekharAuthor Information Division of Pharmaceutical Evaluation I, Office of Clinical Pharmacology and Biopharmaceutics, U.S. Food and Drug Administration, Rockville, MD. Address for correspondence: Division of Pharmaceutical Evaluation I, Office of Clinical Pharmacology and Biopharmaceutics (HFD-860), U.S. Food and Drug Administration, Room 4079, Woodmont Office Center II, 1451 Rockville Pike, Rockville, MD 20852, USA; e-mail: [email protected] American Journal of Therapeutics: March-April 2001 - Volume 8 - Issue 2 - p 109-116 Buy Abstract This analysis was carried out to compare the predictive performance of two different approaches of allometry for the prediction of maximum tolerated dose (MTD) in humans from animal data. The two approaches used to predict MTD in humans in this analysis were (1) the use of a fixed exponent of 0.75 and the LD10 in mice and (2) the use of the LD10 or MTD data from at least three animal species (interspecies scaling). Twenty-five anticancer drugs were taken from the literature and used in this analysis. The results of the study indicate that MTD can be predicted more accurately using interspecies scaling than using a fixed exponent of 0.75. Incorporation of a correction factor known as mean life-span potential can also be used for the improved prediction of MTD for some drugs. One third of the predicted MTD from interspecies scaling can be used as a starting dose in humans. This approach will save time and avoid many unnecessary steps in attaining MTD in humans. © 2001 Lippincott Williams & Wilkins, Inc.