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

IF 2

EJC paediatric oncology Pub Date : 2026-06-01 Epub Date: 2026-02-27 DOI:10.1016/j.ejcped.2026.100499

Ivy A.E. Ankone , Tirsa de Kluis , Lidwien M. Hanff , Antoinette Jaspers-Bakker , Ronald R. de Krijger , Jesse J. Swen , Kathalijne A. Oudhoff , Marieke J.M. Meijs , Max M. van Noesel , Alwin D.R. Huitema , Meta H.M. Diekstra

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Abstract

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.

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米托坦在小儿肾上腺皮质癌中的药代动力学变异性和CYP2B6基因型的作用：一个儿科病例系列

尽管对米托坦进行治疗药物监测，但实现目标血浆浓度仍然具有挑战性。通常报道的参与米托坦代谢的酶是细胞色素P450 (CYP)3A4和2B6，其中CYP2B6具有高度多态性。我们评估了CYP2B6基因型对6例患者达到治疗浓度的影响。我们观察了中间、正常和快速代谢基因型。中间或正常代谢物均达到治疗浓度，剂量在3.5-5.5 g/m2/天之间。尽管给药剂量高达8.0 g/m2/天，快速代谢物仍未达到治疗浓度。这些结果表明CYP2B6基因型可能影响米托坦在小儿肾上腺皮质癌中达到和维持治疗浓度所需的剂量。

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来源期刊

EJC paediatric oncology

CiteScore

0.20

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0.00%

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