pyrimidinones and Opioid-Related-Disorders

A study was designed to determine the interactions, both clinical and pharmacokinetic, between methadone and lopinavir-ritonavir. Results demonstrated a 36% reduction in the methadone area under the plasma concentration-time curve after the introduction of lopinavir-ritonavir, with no coincident symptoms of opioid withdrawal and no requirement for methadone dose adjustment.

Topics: Adult; Analgesics, Opioid; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lopinavir; Male; Methadone; Opioid-Related Disorders; Pyrimidinones; Ritonavir; RNA, Viral; Substance Withdrawal Syndrome

We examined drug interactions between buprenorphine, an opioid partial agonist available by prescription for treatment of opioid dependence, and the protease inhibitors (PIs) nelfinavir (NFV), ritonavir (RTV), and lopinavir/ritonavir (LPV/R). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (n=10 per PI) participated in 24-h pharmacokinetic studies, before and after administration of each PI. Symptoms of opiate withdrawal and excess were determined before and after PI administration. PI pharmacokinetics were determined and compared between opiate-dependent participants and healthy control participants (n=15 per PI). Administration of RTV, but not of NFV or LPV/R, resulted in a significant increase in the buprenorphine area under the concentration-time curve (AUC). Symptoms of opiate excess, however, were not observed. Buprenorphine had no significant effects on PI AUC. Adjustments of doses of either buprenorphine or NFV, LPV/R, or RTV are not likely to be necessary when these drugs are administered for the treatment of opioid dependence and HIV disease.

Topics: Adult; Buprenorphine; Case-Control Studies; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; HIV Protease Inhibitors; HIV Seronegativity; Humans; Lopinavir; Male; Narcotic Antagonists; Nelfinavir; Opioid-Related Disorders; Probability; Pyrimidinones; Reference Values; Risk Assessment; Ritonavir

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.

Topics: HIV Infections; HIV Protease Inhibitors; Humans; Lopinavir; Methadone; Narcotics; Opioid-Related Disorders; Pyrimidinones; Ritonavir; Substance Withdrawal Syndrome

Topics: Adult; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Buprenorphine; Child; Drug and Narcotic Control; Drug Combinations; Drugs, Investigational; HIV Infections; HIV Protease Inhibitors; Humans; Infant; Leukemia, Promyelocytic, Acute; Lopinavir; Opioid-Related Disorders; Oxides; Pyrimidinones; Receptors, Opioid; Ritonavir; United States; United States Food and Drug Administration