PHARMACOKINETICS OF METHADONE AND ITS PRIMARY METABOLITE IN 20 OPIATE ADDICTS

被引:80
作者
DEVOS, JW
GEERLINGS, PJ
VANDENBRINK, W
UFKES, JGR
VANWILGENBURG, H
机构
[1] UNIV AMSTERDAM,ACAD MED CTR,DEPT PHARMACOL,1100 DE AMSTERDAM,NETHERLANDS
[2] JELLINEK CTR,AMSTERDAM,NETHERLANDS
[3] AMSTERDAM INST ADDICT RES,AMSTERDAM,NETHERLANDS
关键词
METHADONE; OPIATE ADDICTS; METHADONE METABOLITE; STEADY-STATE PHARMACOKINETICS; ONE-COMPARTMENT MODEL; 2-COMPARTMENT MODEL;
D O I
10.1007/BF00194951
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts. After administration of the daily oral dose of methadone HCl (mean 60 mg, range 10-225 mg) blood samples were taken and analysed, using a newly developed high-performance liquid chromatography (HPLC) method. The steady-state plasma concentrations of the 20 subjects varied from 65-630 ng . ml(-1) and from 5 to 55 ng . ml(-1), whereas the peak concentrations were 124-1255 ng . ml(-1) and 10-301 ng . ml(-1) for methadone and EDDP, respectively. The calculated ratios between the area under the curve (AUC((0-24) (h))) for methadone and the AUC((0-24) (h)) for EDDP varied from 5.9 to 44.6, indicating interindividual differences in metabolic activity. In 19 out of 20 subjects the pharmacokinetics of methadone are best described using a two-compartment model. The mean body clearance was 1.64 ml . min(-1). kg(-1), whereas the mean elimination rate constant (beta) and plasma half-life (t(1/5)beta) were 0.026 . h(-1) (range 0.013-0.053 . h(-1)) and 31.2 h (range 13-53 h), respectively. Differences of gender were also found. A poor correlation was found between the methadone dose and the steady-state level. A much better correlation was found between the normalized steady-state level and the body clearance.
引用
收藏
页码:361 / 366
页数:6
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