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Titolo:
Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility
Autore:
Wolff, K; Rostami-Hodjegan, A; Hay, AWM; Raistrick, D; Tucker, G;
Indirizzi:
Inst Psychiat, Natl Addict Ctr, London SE5 8AF, England Inst Psychiat London England SE5 8AF Addict Ctr, London SE5 8AF, England Univ Sheffield, Sect Mol Pharmacol & Pharmacogenet, Sheffield S10 2TN, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2TN S Yorkshire, England Univ Leeds, Res Sch Med, Leeds, W Yorkshire, England Univ Leeds Leeds W Yorkshire England ch Med, Leeds, W Yorkshire, England Leeds Addict Unit, Leeds, W Yorkshire, England Leeds Addict Unit Leeds W Yorkshire England Leeds, W Yorkshire, England
Titolo Testata:
ADDICTION
fascicolo: 12, volume: 95, anno: 2000,
pagine: 1771 - 1783
SICI:
0965-2140(200012)95:12<1771:PPAFMM>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAINTENANCE TREATMENT; PROTEASE INHIBITORS; CYTOCHROME-P450 3A4; ADAPTIVE-CHANGES; FATAL METHADONE; PLASMA; OVERDOSE; SYMPTOMS; BINDING; DEATHS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Clinical Medicine
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Wolff, K Inst Psychiat, Natl Addict Ctr, 4 Windsor Walk,Denmark Hill, London SE5 8AF, England Inst Psychiat 4 Windsor Walk,Denmark Hill London England SE5 8AF
Citazione:
K. Wolff et al., "Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility", ADDICTION, 95(12), 2000, pp. 1771-1783

Abstract

Aims. There is evidence that plasma methadone measurements may be of benefit in dosage adjustment during methadone maintenance treatment for opiate dependence. However, to dare the kinetics of oral rac-methadone have been poorly characterized. We describe plasma methadone concentration-time data collected from 35 opiate addicts. Subjects. Oral doses of rac-methadone were given to 24 male and 11 female addicts attending a community-based drug treatment centre. Measurements. Plasma methadone concentrations were measured by liquid chromatography (HPLC). Procedures. Plasma concentration-time datawere collected from patients prescribed oral rac-methadone in order to describe the complex kinetics of the drug incorporating its long elimination half-life. Findings. Auto-induction of methadone metabolism was demonstratedand it was observed that clearance of methadone was significantly lower (p< 0.05) in opiate addicts at the start of treatment (median elimination half-life, 128-hours) than in those who had reached steady-stare (median elimination half-life, 48 hours). Our data has provided the basis for a population-based pharmacokinetic (POP-PK) model which is intended for use as a clinical tool in association with plasma measurements in methadone maintenancepatients. Conclusions. Using plasma monitoring in combination with the application of Bayesian forecasting it should be possible to predict trough levels of methadone during daily dosing. The model is able to utilize sparse sampling, and two blood samples are expected to be sufficient to define patient compliance. Random samples during treatment could be used to assess methadone dosing by comparing predicted with observed measurements for each individual. The clinical tool could therefore help to defect incomplete (failure to consume the whole daily dose as prescribed) and poor (due to ingestion of extra illicit methadone) compliance as wed as therapeutic failure due to drug-drug interactions. Targeting resources in this way could be a cost-effective tool for supervision of methadone dosing.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 05:35:27