The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients.
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.
McCance-Katz
Elinore F
EF
Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA. emccancekatz@vcu.edu
Rainey
Petrie M
PM
Friedland
Gerald
G
Jatlow
Peter
P
D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir; D008691:Methadone / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage; D009293:Opioid-Related Disorders; D011744:Pyrimidinones / Q000009:adverse effects* / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects* / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
D017320:HIV Protease Inhibitors; D009294:Narcotics; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir; D008691:Methadone