Pharmacogenetic Parameters May Determine Correlations of Patients' Methadone Dose and Plasma Levels of Its Metabolites
Ray H. Liu Department of Medical Laboratory Science and Biotechnology
Fooyin University
China
Abstract:
Plasma concentrations of methadone and its metabolite (EDDP), determined by GC-MS, were found to vary among patients receiving the same dosage. Pharmacogenetic parameters' role in the absorption and distribution of these analytes were studied to potentially improve the effectiveness and safeness of methadone maintenance programs. Within a 55-patient group receiving daily dosage in the 10-165 mg range, relatively good correlations between dosage and plasma levels of methadone (r2 = 0.64) and EDDP (r2 = 0.68) were found for the low-dose subgroup (<50 mg/day). Corresponding correlations for the high-dose subgroup (≥50 mg/day) were r2 = 0.14 and r2 = 0.10. Further examining the latter subgroup's pharmacogenetic parameters, we found (a) patients with 2677T/A (in ABCB1) were associated with high EDDP plasma level (p = 0.003); (b) patients with 681A and 990T (in CYP2C19) were associated with low EDDP plasma level (p = 0.015 and 0.010, respectively); and (c) no definite pattern of plasma drug concentration could be established (p > 0.05) for patients with SNP C1236T and C3435T (in ABCB1). Preliminarily data indicated certain pharmacogenetic parameters could determine the correlation of methadone dose and the patients' plasma levels of methadone and EDDP.
