OBJECTIVE: The aim of this study was to assess the potential impact of the pharmacogenetic variability of CYP2B6 and ABCB1 genes on the pharmacokinetics of mitotane. METHODS: A retrospective analysis was carried out on 27 patients with adrenocortical carcinoma on postoperative adjunctive mitotane. CYP2B6 and ABCB1 polymorphisms were genotyped and tested for an association with plasma trough concentration after 3, 6, 9, and 12 months of therapy. RESULTS: Patients with the GT/TT genotype had higher mitotane plasma concentrations compared with patients with GG at 3 months (14.80 vs. 8.01 μg/ml; P=0.008) and 6 months (17.70 vs. 9.75 μg/ml; P=0.015). Multivariate logistic regression analysis showed that only the CYP2B6 rs3745274GT/TT genotype (odds ratio=10.7; P=0.017) was a predictor of mitotane plasma concentrations of at least 14 µg/ml after 3 months of treatment. Mitotane concentrations were not influenced by the polymorphisms of the ABCB1 gene. CONCLUSION: Evaluation of the CYP2B6 polymorphism enabled prediction of the individual response to adjuvant mitotane treatment.
OBJECTIVE: The aim of this study was to assess the potential impact of the pharmacogenetic variability of CYP2B6 and ABCB1 genes on the pharmacokinetics of mitotane. METHODS: A retrospective analysis was carried out on 27 patients with adrenocortical carcinoma on postoperative adjunctive mitotane. CYP2B6 and ABCB1 polymorphisms were genotyped and tested for an association with plasma trough concentration after 3, 6, 9, and 12 months of therapy. RESULTS:Patients with the GT/TT genotype had higher mitotane plasma concentrations compared with patients with GG at 3 months (14.80 vs. 8.01 μg/ml; P=0.008) and 6 months (17.70 vs. 9.75 μg/ml; P=0.015). Multivariate logistic regression analysis showed that only the CYP2B6 rs3745274GT/TT genotype (odds ratio=10.7; P=0.017) was a predictor of mitotane plasma concentrations of at least 14 µg/ml after 3 months of treatment. Mitotane concentrations were not influenced by the polymorphisms of the ABCB1 gene. CONCLUSION: Evaluation of the CYP2B6 polymorphism enabled prediction of the individual response to adjuvant mitotane treatment.
Authors: Anyue Yin; Madeleine H T Ettaieb; Jesse J Swen; Liselotte van Deun; Thomas M A Kerkhofs; Robert J H M van der Straaten; Eleonora P M Corssmit; Hans Gelderblom; Michiel N Kerstens; Richard A Feelders; Marelise Eekhoff; Henri J L M Timmers; Antonio D'Avolio; Jessica Cusato; Henk-Jan Guchelaar; Harm R Haak; Dirk Jan A R Moes Journal: Clin Pharmacokinet Date: 2021-01 Impact factor: 6.447
Authors: Nada El Ghorayeb; Geneviève Rondeau; Mathieu Latour; Christian Cohade; Harold Olney; André Lacroix; Paul Perrotte; Alexis Sabourin; Tania L Mazzuco; Isabelle Bourdeau Journal: Medicine (Baltimore) Date: 2016-03 Impact factor: 1.889
Authors: Sarah Allegra; Soraya Puglisi; Irene Brescia; Francesco Chiara; Vittoria Basile; Anna Calabrese; Giuseppe Reimondo; Silvia De Francia Journal: Life (Basel) Date: 2021-03-23