ABCB1 genetic polymorphisms affect opioid requirement by altering function of the intestinal P-glycoprotein.

Autor: Qin W; Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China., Zhang L; Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China., Wang X; Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China., Liu B; Department of Pain Management, China-Japan Friendship Hospital, Beijing 100029, China., Xu L; Department of Pain Management, China-Japan Friendship Hospital, Beijing 100029, China., Liu L; Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: liulihong@zryhyy.com.cn., Fan B; Department of Pain Management, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: fanbifa@zryhyy.com.cn.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Jul; Vol. 176, pp. 116897. Date of Electronic Publication: 2024 Jun 08.
DOI: 10.1016/j.biopha.2024.116897
Abstrakt: The association between polymorphisms of the human ATP binding cassette subfamily B member 1 (ABCB1) gene and opioid response has attracted intense attention recently. As the ABCB1 gene encodes for the transporter P-glycoprotein in the brain and intestine involved in the pharmacokinetics of opioids, we investigated the effects of ABCB1 genetic polymorphisms on doses of opioids for pain relief and determined which pharmacokinetic process was affected in cancer pain patients. Sixty-eight cancer pain patients admitted for intrathecal therapy (ITT) were included. The association between ABCB1 genetic polymorphisms (C3435T, C1236T, G2677T/A and A61G) and systemic doses of opioids before ITT were investigated. Concentrations of oxycodone in plasma and cerebrospinal fluid (CSF) were determined by HPLC-MS/MS in 17 patients treated with oral oxycodone before ITT, and the influences of ABCB1 genetic polymorphisms on plasma-concentration to oral-dose ratios and CSF-concentration to plasma-concentration ratios of oral oxycodone were further analyzed. ABCB1 C3435T and G2677T/A polymorphisms were significantly associated with systemic doses of opioids before ITT, which coincided with the influences of ABCB1 C3435T and G2677T/A polymorphisms on the ratios of plasma-concentration to oral-dose. However, no significant difference was found in ratios of CSF-concentration to plasma-concentration among ABCB1 SNP genotypes. The present study provided the first evidence that ABCB1 C3435T and G2677T/A polymorphisms affect opioid requirement in cancer pain patients via altering transportation function of P-glycoprotein in the intestine, which will further expand our knowledge about pharmacokinetics of opioids and could contribute to the individualization of opioids use.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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