Abstract | BACKGROUND: METHODS: Blood samples for PK and PD assessment were collected. A semi-mechanistic nonlinear mixed effect PK/PD model was successfully developed to characterize enasidenib plasma PK and to assess enasidenib-induced CYP3A activity. RESULTS: The PK model showed that enasidenib plasma concentrations were adequately described by a one-compartment model with first-order absorption and elimination; the PD model showed a high capacity to induce CYP3A (Emax=7.36) and a high enasidenib plasma concentration to produce half of maximum CYP3A induction (EC50 =31,400 ng/mL). Monte Carlo simulations based on the final PK/PD model showed that at 100 mg once daily dose there was significant drug accumulation and a maximum of three-fold CYP3A induction after multiple doses. Although the EC50 value for CYP3A induction by enasidenib is high, CYP3A induction was observed due to significant drug accumulation. CONCLUSION:
CYP3A induction following enasidenib dosing should be considered when prescribing concomitant medication metabolized via this pathway.
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Authors | Yan Li, Jamie N Connarn, Jian Chen, Zeen Tong, Maria Palmisano, Simon Zhou |
Journal | Clinical pharmacology : advances and applications
(Clin Pharmacol)
Vol. 11
Pg. 39-50
( 2019)
ISSN: 1179-1438 [Print] New Zealand |
PMID | 30858735
(Publication Type: Journal Article)
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