Journal Article

The Protease Inhibitor Lopinavir-Ritonavir May Produce Opiate Withdrawal in Methadone-Maintained Patients

Elinore F. McCance-Katz, Petrie M. Rainey, Gerald Friedland and Peter Jatlow

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 37, issue 4, pages 476-482
Published in print August 2003 | ISSN: 1058-4838
Published online August 2003 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/376907
The Protease Inhibitor Lopinavir-Ritonavir May Produce Opiate Withdrawal in Methadone-Maintained Patients

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This study examines the pharmacokinetic/pharmacodynamic interactions between (1) lopinavir-ritonavir (L/R), a fixed combination of protease inhibitors used for the treatment of HIV disease, and (2) ritonavir alone at the same dosage as that in the L/R formulation, with methadone, an opiate frequently used in substance abuse pharmacotherapy for opioid (heroin)–dependent injection drug users, many of whom are infected with HIV. L/R was associated with significant reductions in the methadone area under the concentration-time curve (P < .001), maximum concentration (P < .001), and minimum concentration (P < .001), as well as increased methadone oral clearance (P < .001) and increased opiate withdrawal symptoms (P = .013), whereas ritonavir use alone modestly and nonsignificantly increased methadone concentrations. Lopinavir is a potent inducer of methadone metabolism, and treatment with L/R requires clinical monitoring and increased methadone doses in some patients, whereas ritonavir has no significant effect on methadone metabolism.

Journal Article.  3764 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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