Therapeutic drug monitoring in methadone maintenance therapy (MMT) : an evaluation of genetic factors influencing clinical outcomes and serum concentrations of methadone

摘要

Terapi Gantian Methadone (TGM) telah digunakan secara meluas dan berfungsi untuk mengelakkan berlakunya gejala penarikan dalam kalangan penyalahguna dadah jenis opiat. Ia merupakan salah satu daripada kaedah pendekatan “pengurangan kemudaratan” (harm reduction) bagi menurunkan kadar penularan jangkitan melalui darah dalam komuniti terutamanya HIV AIDS yang boleh membawa maut. Walau bagaimanapun, proses penentuan dos yang optimum bagi setiap pesakit adalah sukar dan mencabar kerana ia menunjukkan kepelbagaian aktiviti farmakologi yang tinggi dalam individu yang berbeza. Kajian ini menghuraikan hubungkait di antara kepekatan methadone darah (Ctrough) dengan dos harian pesakit dan keberkesanan yang dikehendaki iaitu keterukkan gejala penarikan dan ujian pengesahan air kencing bagi pengambilan dadah terlarang. Hubungan antara pelbagai haplotaip gen CYP2B6 dengan kepekatan methadone darah dan variasi polimorfisme nukleotida tunggal OPRM1 (A118G) dengan tahap keberkesanan klinikal yang diukur juga dikaji.ududMethadone maintenance therapy (MMT) has been widely used to prevent withdrawal symptoms among opiate use disorder patients. It is one of the harm reduction approaches in order to reduce the spread of fatally blood borne diseases in the community especially HIV AIDS. However, determining the optimal dose in patients is somehow difficult and challenging as it shows wide inter-individual variability of pharmacological activity. This study correlates the trough serum methadone concentrations (Ctrough) at steady state with the methadone dose and the clinical outcomes namely severity of withdrawal symptoms and urinalysis for other illicit drugs. The relationship between various CYP2B6 haplotypes with the Ctrough and OPRM1 (A118G) single nucleotide polymorphisms (SNPs) with the clinical outcomes measures were also studied.udud