Pharmacokinetic variability of mitotane in pediatric adrenocortical carcinoma and the role of CYP2B6 genotypes: a pediatric case series

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/m 2 /day. The rapid metabolizer did not reach therapeutic concentrations despite receiving up to 8.0 g/m 2 /day. These results indicate CYP2B6 genotypes may affect the dose needed to achieve and maintain therapeutic concentrations of mitotane in pediatric adrenocortical carcinoma.