Farmacogenética del paciente adicto a heroína en tratamiento de deshabituación

Abstract

Introduction: The human and social cost of addiction is very high. For this reason, government organizations implement programs to stop using drugs such as heroin. Heroin withdrawal programs often involve replacement therapy, usually with methadone or buprenorphine/naloxone. These drugs are metabolized by different liver enzymes. The genetic variability related to these enzymes implies pharmacokinetic variations between different drug users. Objectives: To determine the sociodemographic and pharmacogenetic characteristics of patients undergoing treatment for heroin addiction and to determine if the pharmacogenetic profile determines the type of opioid substitution treatment for heroin withdrawal, the methadone dose and the abandonment of the withdrawal program. In addition, to determine if drug interactions influence the methadone dose and discontinuation of the withdrawal program. Material and methods: A prospective experimental study including 191 patients from the southeast of Spain who were part of the heroin withdrawal program with opioid substitution treatment. A survey was conducted where sociodemographic and pharmacological data were collected. In addition, a peripheral blood sample was extracted for the genetic analysis of the marked allele polymorphisms (tag SNPs) of citochrome P450 (CYP) 2B6*6 (rs3745274), 2C9*2 (rs1799853), 2C9*3 (rs1057910), 2D6*4 (rs3892097) and 3A4*1B (rs27405749). KASPar® probes (CYP2B6*6, 2C9*2, 2C9*3 and 3A4*1B) and TaqMan® probes (CYP2D6 * 4) were used for genotyping. Results: Of the 191 patients, 81.2% were men, with a mean age of 43±8 years, and 18.8% were women, with a mean age of 40±9 years. The wild type homozygous (AA) genotypes of the CYP2C9*3 polymorphism and the minority allele (A) of CYP2D6*4 are more frequent in the group requiring low doses of methadone (p=0.053 and p=0.026). The wild-type homozygous (TT) genotype of the CYP2C9*2 polymorphism is more frequent in the group that does not abandon the withdrawal program (p=0.016). The heterozygous genotype (AC) of the CYP2C9*3 polymorphism and the wild type homozygous (AA) genotype of the CYP3A4*1B polymorphism are more frequent in the group leaving the withdrawal program (p=0.020 and p=0.037). In patients who consume CYP2D6 inhibitor drugs, the homozygous minority genotype (AA) of the CYP2D6*4 polymorphism is more frequent in the group of patients who do not abandon the withdrawal program (p=0.059). Conclusions: The profile of patient in treatment for a heroin addiction in the southeast of Spain corresponds with a middle-aged man, who consumes other drugs and has a daily heroin consumption of a quarter of a gram. Genetic polymorphisms for CYP2B6*6, 2C9*3 and 2D6*4 determine the methadone dose for a heroin withdrawal treatment. Genetic polymorphisms for CYP2C9*2, 2C9*3 and 3A4*1B are related to the abandonment of the withdrawal program. The genetic polymorphisms analyzed do not determine the withdrawal treatment with methadone or buprenorphine / naloxone. In patients who use CYP2D6 inhibitor drugs, the presence of the minor homozygous genotype for variant *4 implies less abandonment of the withdrawal program. The determination of the genetic variants of cytochrome P450 could be useful in the management of the withdrawal treatment in a heroin-addicted patient