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Open access

Tatjana Petrushevska

Abstract

The aim of this review is to give new emphasis to key aspects of the proposed treatment of drug addiction. Surveys for so called “second-line” treatment of drug addiction, with heroin (diacetylmorphine) as a pharmaceutical preparation, started since 1990, but this issue is becoming particularly popular in the last period. Drug addiction according to WHO and International Classification of Diseases (ICD10) is chronic, relapsing disease characterized by compulsive drug seeking and use despite harmful consequences as well as neurochemical and molecular changes in the brain. Drugs generate crime, violence and other social problems that are damaging society as a whole. Drug addiction is medical disorder to which contributes more factors and it is necessary to implement the treatment in multi disciplinary manner - from pharmacological, psychiatric, and social aspect. In recent periods studies are carrying out in several countries in the European region, to provide justification, with the scientific medical evidence, for use of heroin as a pharmaceutical dosage form, for treatment of drug addictions for previously unresponsive group. This review paper is focused on maintenance treatment with heroin, retention of the patients into treatment, whether the dose that is expected to be effective at the same time is safe, which organ (systems) are involved in eliminating the drug from the body, whether the injection is the best way for application of the drug. Purpose of this review paper is not to be supporter or opponent, but to inform, transparently to discuss all aspects and to set conclusions about this type of treatment, within national strategy context.

Open access

Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai and Supeecha Wittayalertpanya

Abstract

Background

Cytochrome P450 (CYP) 3A5 is a major isoform metabolizing tacrolimus. Individual variation in the metabolism may result from CYP3A5 single nucleotide polymorphisms (SNPs). CYP3A5*3 polymorphism is strongly associated with tacrolimus pharmacokinetic variations in 65%–85% of Asian populations. A minor polymorphism related to requirement for tacrolimus is the POR*28 mutation, which increases in vivo CYP3A activity for tacrolimus. These two SNPs might affect individual maintenance dosages of tacrolimus.

Objectives

To determine the association of CYP3A5*3 and POR*28 SNPs with maintenance dosage requirements for tacrolimus in Thai recipients of kidney transplants.

Methods

We enrolled 150 Thai recipients of kidney transplants. Clinical laboratory data were recorded 3 months after first administration of tacrolimus. Two SNPs; rs776746 A > G (CYP3A5*3 allele) and rs1057868 C > T (POR*28 allele) were assessed. All 300 genotypes were analyzed by real-time polymerase chain reactions.

Results

Recipients were classified into 9 groups according to possible matching genotypes. The mean dosage required for the maintenance phase was significantly higher in the CYP3A5*1 allele or CYP3A5 expressers (groups 1-6, 0.163, 0.167, 0.141, 0.128, 0.131, and 0.174 mg/kg/day, respectively) than those not expressing CYP3A5*3/*3 or CYP3A5 (groups 7-9, 0.081, 0.073, and 0.069 mg/kg/day, respectively, P < 0.05). When the mean dosage was compared under POR*28 one or two alleles in CYP3A5 expressers, P was significantly smaller than in CYP3A5 expressers with POR*1/*1.

Conclusions

CYP3A5 polymorphism is key to determining tacrolimus dosage requirements during the maintenance phase in kidney transplant recipients and POR*28 may contribute to the interindividual variability