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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/FPC.0b013e3283606cb2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacogenomic landscape of the Thai population from genome sequencing of 949 individuals.
Sci Rep
December 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.
View Article and Find Full Text PDFRelationships among CYP2B6 genetic variants and serum levels of multiple polychlorinated biphenyls and hydroxylated metabolites in a Japanese population.
J Hazard Mater
December 2024
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo, Kyoto 606-8501, Japan. Electronic address:
Article Synopsis
- Production of polychlorinated biphenyls (PCBs) has been banned since 2001, but health risks from exposure continue due to their metabolism by enzymes like CYP2B6, where gene polymorphisms may influence this process.
- The study analyzed blood samples from 129 individuals to explore the relationship between specific CYP2B6 gene variants and levels of PCBs and their metabolites (OH-PCBs), finding variations in metabolism linked to different genotypes, particularly *1/*4 and *6/*6.
- Results showed that the *1/*4 genotype was correlated with higher metabolite-to-parent compound ratios for certain PCBs, while the *6/*6 genotype showed the opposite effect, indicating complex interactions between genetic factors
Pharmacogenomic variation and sedation outcomes during early intensive care unit admission: A pragmatic study.
Clin Transl Sci
December 2024
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Unpredicted responses to sedatives and analgesics are common in critically ill patients on mechanical ventilation (MV) and may be attributed to genetic variation. Our primary aim was to investigate the association between the pharmacogenomic (PGx) variation and sedation outcomes. The secondary aim was to capture intensive care unit (ICU) participants' perceptions of PGx.
View Article and Find Full Text PDFResearch on genetic variant characteristics in ADME genes based on whole-exome sequencing in the Han Chinese population.
Eur J Pharm Sci
December 2024
Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, China. Electronic address:
Background: Genetic variants in absorption, distribution, metabolism, and excretion (ADME) genes affect drug efficacy and side effects. Whole-exome sequencing (WES) effectively identifies these variants. Findings from Western populations may not apply to the Han Chinese population due to ethnic differences.
View Article and Find Full Text PDFMethadone metabolism and cytochrome P450 polymorphisms: a systematic review and meta-analysis.
Expert Opin Drug Metab Toxicol
November 2024
Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA.
Introduction: Confusion regarding methadone metabolism exists, hampering optimal clinical use. A systematic review was conducted to assess the impacts of cytochrome P450 (CYP) genetic polymorphisms on methadone outcomes.
Methods: MEDLINE, EMBASE, Web of Science, PsycINFO, and CENTRAL were searched to identify studies reporting methadone dose-adjusted plasma concentrations, clearance, maintenance dose, or treatment response in relation to polymorphisms in humans.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!