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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 < 0.001 ), maximum concentration (p<0.001 ), and minimum concentration (p<0.001 ), as well as increased methadone oral clearance (p<0.001 ) and increased opiate withdrawal symptoms (p=0.13), whereas ritonavir use alone modestly and nonsignificantly increased methadone concentration
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.
McCance-Katz EF, Rainey PM, Friedland G, Jatlow P. The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients. Clinical Infectious Diseases. 2003; 4: 476-482.