Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia.

Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia. J Clin Pharmacol. 2020 Jun 29;: Authors: Kang D, Ludwig E, Jaworowicz D, Huang H, Fiedler-Kelly J, Cortes J, Ganguly S, Khaled S, Krämer A, Levis M, Martinelli G, Perl A, Russell N, Abutarif M, Choi Y, Mendell J, Yin O Abstract Quizartinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor that has shown robust clinical activity in patients with FLT3-internal tandem duplication-mutated relapsed/refractory acute myeloid leukemia (AML). This analysis evaluated the population pharmacokinetics (PK) of quizartinib and its active metabolite, AC886, in a pooled analysis of data from 649 healthy volunteers or patients with AML from 8 clinical trials including the phase 3 QuANTUM-R study. Quizartinib was given as a single dose or multiple once-daily doses of 20, 30, 60, or 90 mg. Nonlinear mixed-effects modeling was performed using observed concentrations of quizartinib and AC886. Strong CYP3A inhibitor use resulted in an 82% increase in the area under the curve (AUC) and a 72% increase in the maximum concentration (Cmax ) of quizartinib. Albumin level, age, and body surface area were statistically significant covariates on quizartinib PK. However, their individual effects on quizartinib AUC and Cmax were <20%. For AC886, strong CYP3A inhibitor use, patient status, body surface area, and black/African Ameri...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research