TY - JOUR
T1 - Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes
T2 - a pediatric case series
AU - Ankone, Ivy A.E.
AU - de Kluis, Tirsa
AU - Hanff, Lidwien M.
AU - Jaspers-Bakker, Antoinette
AU - de Krijger, Ronald R.
AU - Swen, Jesse J.
AU - Oudhoff, Kathalijne A.
AU - Meijs, Marieke J.M.
AU - van Noesel, Max M.
AU - Huitema, Alwin D.R.
AU - Diekstra, Meta H.M.
N1 - Publisher Copyright:
© 2026 The Authors
PY - 2026/6
Y1 - 2026/6
N2 - Despite therapeutic drug monitoring of mitotane, achieving target plasma concentrations remains challenging. Commonly reported enzymes involved in mitotane metabolism are cytochrome P450 (CYP)3A4 and 2B6, with CYP2B6 being highly polymorphic. We evaluated the impact of CYP2B6 genotypes on achieving therapeutic concentrations in six patients. We observed intermediate, normal, and rapid metabolizer genotypes. Intermediate or normal metabolizers all reached therapeutic concentrations, receiving between 3.5–5.5 g/m2/day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m2/day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.
AB - Despite therapeutic drug monitoring of mitotane, achieving target plasma concentrations remains challenging. Commonly reported enzymes involved in mitotane metabolism are cytochrome P450 (CYP)3A4 and 2B6, with CYP2B6 being highly polymorphic. We evaluated the impact of CYP2B6 genotypes on achieving therapeutic concentrations in six patients. We observed intermediate, normal, and rapid metabolizer genotypes. Intermediate or normal metabolizers all reached therapeutic concentrations, receiving between 3.5–5.5 g/m2/day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m2/day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.
KW - Adrenocortical carcinoma
KW - Cancer
KW - Cytochrome P-450 CYP2B6
KW - Mitotane
KW - Pediatrics
UR - https://www.scopus.com/pages/publications/105031745187
UR - https://www.mendeley.com/catalogue/bc26491f-fd71-3f55-86c3-b48a30c591e8/
U2 - 10.1016/j.ejcped.2026.100499
DO - 10.1016/j.ejcped.2026.100499
M3 - Article
AN - SCOPUS:105031745187
SN - 2772-610X
VL - 7
JO - EJC Paediatric Oncology
JF - EJC Paediatric Oncology
M1 - 100499
ER -