Association between Pk/Pd-Involved Gene Polymorphisms and Carbamazepine-Individualized Therapy

Abstract

Aim: To evaluate the association between the major genetic variants involved in the pharmacokinetic/pharmacodynamic (PK/PD) properties of carbamazepine (CBZ) and its maintenance doses and concentrations. Patients & methods: The genotypes of 166 patients receiving CBZ monotherapy were detected using high-resolution melting curve (HRM) and TaqMan methods. Results: Both univariate and multiple regression analyses revealed that carriers of the SCN1A IVS5–91G>A or EPHX1 c.337T>C allele tended to require a higher CBZ dose and a lower CBZ natural logarithmic concentration–dose ratio (lnCDR) than noncarriers (< 0.05). Furthermore, two interactions between these genes were associated with the lnCDR and the maintenance dosage of CBZ, respectively. Conclusion:SCN1A IVS5–91G>A gene polymorphism is potential genetic biomarker associated with the PK of CBZ.

Keywords::

• ABCC2
• carbamazepine
• carbamazepine 10,11-epoxide
• EPHX1
• epilepsy
• genetic polymorphisms
• SCN1A

Acknowledgements

The authors sincerely thank the medical staff from the Huashan Hospitals of Shanghai, China, for their help and collaboration, as well as our patients. The authors highly appreciate Prof Jian-Feng Luo for the assistance with statistical analysis.

Financial & competing interests disclosure

This project was supported by a grant from the Natural Science Foundation of Shanghai, China (grant number 14ZR1404800). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or a financial conflict with the subject matter or the materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human and animal experimental investigations. In addition, for the investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This project was supported by a grant from the Natural Science Foundation of Shanghai, China (grant number 14ZR1404800). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or a financial conflict with the subject matter or the materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.