Pharmacologically Guided Dose Escalation

90% inhibitory concentration (ICgo) for bone marrow or tumor cells. 

There is enormous scatter in the ratio of human murine tolerable doses. Thus, while murine doses may seem to give reasonable predictions for acceptable human doses on the average, there is no predictive consistency that could be relied upon for any specific drug about to enter Phase I study. 

The drug exposure (area under the curve AUC) ratio at approximately equitoxic doses has much less variability, indicating that pharmacokinetic differences account for almost all of the differences observed for toxic doses of this set of drugs between humans and mice. 

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