Pharmacokinetics (PK) plays a critical role during IND and NDA evaluation at US FDA.There are a few areas where PK exposure parameters are used for safety assessment.The first in-human study is a milestone transition from drug discovery to drug development.The AUC values at NOAEL levels from animal toxicokinetics (TK) studies provide the threshold, for which the human systemic exposure should not exceed during Phase 1 dose escalation studies.The ratio of the AUC at NOAEL from animal toxicology studies to the AUC at the therapeutic dose in humans represents a safety margin.Bioavailability data is required for NDAs, which is a filing issue for 505(b)(2) NDAs.A new drug with the strong CYP inhibition is not desired.There are such drugs that have been withdrawn from US market.