Clinical toxicology of drugs used in the treatment of opiate dependency

FRANÇAIS :
Les études portant sur la cinétique des substances administrées lors des cures de sevrage des sujets opio-dépendants ont été trop négligées : méthadone, acétylméthadol, buprénorphine, naltrexone et clonidine. Bien que la méthadone soit utilisée depuis une trentaine d'année chez les toxicomanes, sa cinétique semble plutôt défavorable. La naltrexone serait le produit le plus intéressant sous cet angle mais l'observance demeure médiocre car elle n'a aucun effet agoniste. L'usage de ces substances augmentant, il serait souhaitable de développer des techniques fiables permettant de vérifier le suivi du traitement. [Résumé Toxibase]
ENGLISH:
Many aspects of the pharmacokinetics of methadone have been evaluated since 1970. Analytic techniques used to monitor urine and serum or plasma concentrations of methadone and its metabolites have improved with advances in chromatography and development of immunoassay techniques. On reviewing the literature on methadone since 1970, however, there were several recurring limitations of the experimental design in a large number of the studies reported. These include: 1. No appreciation for the effect of urinary pH on excretion of methadone 2. Small number of patients enrolled with inadequate control subjects 3. The effect of smoking cigarettes was not evaluated or adequately controlled 4. Urine collections were often obtained without supervision and correcting results to creatinine excretion 5. Blood specimens were generally not collected from 0-15 minutes after intravenous dosing 6. Incomplete excretion data (nonhydrolysis of glucuronide conjugates) in the urine 7. Most studies did not evaluate protein binding of methadone when attempting to correlate therapeutic control or failure with serum concentrations of methadone. In general, the literature supporting the use of naltrexone was more favorable than for methadone, buprenorphine, LAAM, and clonidine. The major limitation on the use of naltrexone, however, is the lack of incentive for the patient to keep taking the medication. If the use of naltrexone, LAAM, buprenorphine, or clonidine becomes widely available, robust analytic techniques must be developed for monitoring of these drugs, their metabolites, or both in the urine to verify patient compliance.