细胞色素P450 2D6超快速代谢与血液中吗啡/可待因比值：是可待因还是海洛因？

CYP2D6 ultrarapid metabolism and morphine/codeine ratios in blood: was it codeine or heroin?

作者信息

He Y J, Brockmöller J, Schmidt H, Roots I, Kirchheiner J

机构信息

Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany.

出版信息

J Anal Toxicol. 2008 Mar;32(2):178-82. doi: 10.1093/jat/32.2.178.

DOI:10.1093/jat/32.2.178

PMID:18334103

Abstract

The concentration ratio of morphine (Mor) over codeine (Cod) in opiate positive blood samples is used to discriminate between the use of illegal heroin (high ratios) and therapeutic codeine (low ratios). However, genetically caused CYP2D6 ultra-rapid metabolism might lead to Mor/Cod comparable to heroin intake. A single oral dose of 30 mg codeine was administered to 11 CYP2D6 ultrarapid metabolizers (UMs) and 12 extensive metabolizers (EMs). Codeine and its morphine metabolites and Mor/Cod were quantified in plasma and urine by liquid chromatography with tandem mass spectrometry within 24 h after codeine intake. The Mor/Cod in plasma were below 1 for both UMs and EMs during the first 12 h. After 12 h, 9% of the 11 UM and none of the 12 EM had ratios > 1. In urine, Mor/Cod ratios were below one for all EMs and UMs during the first 12 h. Thus, CYP2D6 genotyping in general will not explain Mor/Cod ratios > 1 in plasma or urine, unless the time of drug intake is more than 24 h previous.

摘要

阿片类阳性血样中吗啡（Mor）与可待因（Cod）的浓度比用于区分非法海洛因的使用（高比值）和治疗性可待因的使用（低比值）。然而，基因导致的CYP2D6超快速代谢可能导致Mor/Cod比值与海洛因摄入量相当。对11名CYP2D6超快速代谢者（UMs）和12名广泛代谢者（EMs）单次口服30mg可待因。在可待因摄入后24小时内，通过液相色谱-串联质谱法对血浆和尿液中的可待因及其吗啡代谢产物以及Mor/Cod进行定量。在前12小时内，UMs和EMs血浆中的Mor/Cod均低于1。12小时后，11名UMs中有9%的比值>1，而12名EMs中无一例比值>1。在尿液中，所有EMs和UMs在前12小时内的Mor/Cod比值均低于1。因此，一般来说，CYP2D6基因分型无法解释血浆或尿液中Mor/Cod比值>1的情况，除非药物摄入时间超过24小时。