| Title | The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients. |
| Publication Type | Journal Article |
| Year of Publication | 2003 |
| Authors | McCance-Katz, Elinore F., Petrie M. Rainey, Gerald Friedland, and Peter Jatlow |
| Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America |
| Volume | 37 |
| Issue | 4 |
| Pagination | 476-82 |
| Date Published | 2003 Aug 15 |
| ISSN | 1537-6591 |
| Keywords | HIV Infections, HIV Protease Inhibitors, Humans, Lopinavir, Methadone, Narcotics, Opioid-Related Disorders, Pyrimidinones, Ritonavir, Substance Withdrawal Syndrome |
| Abstract | 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. |
| Alternate Journal | Clin. Infect. Dis. |
