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Dolutegravir does not affect methadone pharmacokinetics in opioid-dependent, HIV-seronegative subjects.
- Source :
-
Drug and alcohol dependence [Drug Alcohol Depend] 2013 Dec 01; Vol. 133 (2), pp. 781-4. Date of Electronic Publication: 2013 Aug 26. - Publication Year :
- 2013
-
Abstract
- Background: Dolutegravir (DTG) is an investigational integrase inhibitor for treatment of HIV infection. As intravenous drug use is a common risk factor for HIV, this study evaluated the effect of DTG on the pharmacokinetics (PK) of methadone.<br />Methods: This was an open-label, 2-period study in adult, opioid-dependent, HIV-seronegative subjects. Subjects received their current individual methadone doses once daily for 3 days (Period 1) followed by DTG 50mg twice daily (BID) for 5 days while continuing their stable methadone therapy (Period 2). Serial PK samples for R- and S-methadone were collected after each Period. Pharmacodynamic (PD) measures and safety assessments were obtained throughout the study. Non-compartmental PK analysis was performed, and geometric least-squares mean ratios and 90% confidence intervals were generated.<br />Results: Plasma exposures of total, R-, and S-methadone were not affected by co-administration of DTG. Mean ratios for AUC were 0.98, 0.95, and 1.01 for total, R-, and S-methadone, respectively, alone compared with in combination with DTG. No statistically significant differences were noted between the 2 treatment periods in methadone PD measures. The combination of DTG and methadone was well tolerated. No deaths, serious adverse events, or grade 3/4 adverse events occurred. No clinically significant changes in laboratory values, vital signs, or electrocardiograms were observed.<br />Conclusion: Co-administration of methadone with repeat doses of DTG 50mg BID had no effect on total, R-, and S-methadone PK or on methadone-induced PD markers. No dose adjustment in methadone is required when given in combination with DTG.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Drug Interactions
Female
HIV Integrase Inhibitors adverse effects
Heterocyclic Compounds, 3-Ring adverse effects
Humans
Male
Methadone adverse effects
Middle Aged
Narcotics adverse effects
Oxazines
Piperazines
Pupil drug effects
Pyridones
Substance Abuse, Intravenous
Substance Withdrawal Syndrome psychology
Young Adult
HIV Integrase Inhibitors pharmacology
HIV Seronegativity
Heterocyclic Compounds, 3-Ring pharmacology
Methadone pharmacokinetics
Narcotics pharmacokinetics
Opiate Substitution Treatment
Opioid-Related Disorders metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0046
- Volume :
- 133
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Drug and alcohol dependence
- Publication Type :
- Academic Journal
- Accession number :
- 24018316
- Full Text :
- https://doi.org/10.1016/j.drugalcdep.2013.08.009