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Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study

Hallinan, Richard ; Crettol, Séverine ; Agho, Kingsley ; Attia, John ; Besson, Jacques ; Croquette-Krokar, Marina ; Hämmig, Robert ; Déglon, Jean-Jacques ; Byrne, Andrew ; Ray, John ; Somogyi, Andrew ; Eap, Chin

In: European Journal of Clinical Pharmacology, 2009, vol. 65, no. 11, p. 1113-1120

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    Titre
    • Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study
    Auteur
    • Hallinan, Richard. The Byrne Surgery, Redfern, NSW, Australia
    • Crettol, Séverine. Unité de Biochimie et Psychopharmacologie Clinique, Centre des Neurosciences Psychiatriques, Département de Psychiatrie-CHUV, Hôpital de Cery, Université de Lausanne, Prilly, Switzerland
    • Agho, Kingsley. School of Medicine, University of Western Sydney, Sydney, NSW, Australia
    • Attia, John. Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW, Australia
    • Besson, Jacques. Centre St-Martin, Département de Psychiatrie-CHUV, Université de Lausanne, Lausanne-Dorigny, Switzerland
    • Croquette-Krokar, Marina. Division d'Abus de Substances, Hôpitaux Universitaire de Genève, Geneva, Switzerland
    • Hämmig, Robert. Universitäre Psychiatrische Dienste Bern, Integrierter Drogendienst, Bern, Switzerland
    • Déglon, Jean-Jacques. Fondation Phénix, Chêne-Bourg, Switzerland
    • Byrne, Andrew. The Byrne Surgery, Redfern, NSW, Australia
    • Ray, John. Division of Clinical Pharmacology and Toxicology, St Vincents Hospital, Darlinghurst, NSW, Australia
    • Somogyi, Andrew. Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
    • Eap, Chin. Unité de Biochimie et Psychopharmacologie Clinique, Centre des Neurosciences Psychiatriques, Département de Psychiatrie-CHUV, Hôpital de Cery, Université de Lausanne, Prilly, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • European Journal of Clinical Pharmacology, 2009, vol. 65, no. 11, p. 1113-1120. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:311663
    Summary
    Purpose: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. Methods: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. Results: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. Conclusion: Cannabis use and higher methadone doses in MMT could in part be a response to—or a cause of—more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MMT