Population Pharmacokinetics of Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E-Mutant Astrocytomas.

Population Pharmacokinetics of Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E-Mutant Astrocytomas. J Clin Pharmacol. 2020 May 31;: Authors: Wang H, Long-Boyle J, Winger BA, Nicolaides T, Mueller S, Prados M, Ivaturi V Abstract Vemurafenib (Zelboraf) is an orally available BRAFV600E inhibitor approved for the treatment of unresectable or metastatic BRAFV600E -mutant melanoma. The primary objective of this work was to characterize the pharmacokinetics (PK) of vemurafenib in pediatric patients with recurrent/refractory astrocytomas harboring the BRAFV600E mutation. The study was also designed to evaluate the feasibility of replacing whole vemurafenib tablets with crushed tablets in young children unable to swallow tablets. Twenty-five pediatric patients (median age, 8.8 years; range, 3.3-19.2) with recurrent/refractory BRAFV600E -mutant astrocytomas received whole (n = 19) or crushed (n = 6) vemurafenib tablets twice daily. Plasma samples were collected on days 1, 15, and 22 in cycle 1 of vemurafenib treatment. Descriptive PK analyses demonstrated significant variability (approximately 6-fold) in drug exposure. A 1-compartment model with first-order absorption and elimination was developed by adjusting the vemurafenib PK model previously validated in adults with mutant BRAFV600E melanoma. After inclusion of allometric scaling on total body weight, the model adequately described the PK of vemurafenib in children betwee...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research