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Effect of Tenofovir Disoproxil Fumarate on the Pharmacokinetics and Pharmacodynamics of Total, R‐, and S‐Methadone
Author(s) -
Smith Patrick F.,
Kearney Brian P.,
Liaw Sandra,
Cloen Denise,
Bullock Julie M.,
Haas Curtis E.,
Yale Kitty,
Booker Brent M.,
Berenson Charles S.,
Coakley Dion F.,
Flaherty John F.
Publication year - 2004
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.24.11.970.36141
Subject(s) - tenofovir , pharmacodynamics , pharmacokinetics , methadone , pharmacology , medicine , human immunodeficiency virus (hiv) , virology
Study Objective. To evaluate the potential effect of tenofovir disoproxil fumarate (DF) on the pharmacokinetics of methadone. Design. Phase I, open‐label, fixed‐sequence, pharmacokinetic drug‐drug interaction study. Setting. Clinical research center. Subjects. Fourteen volunteers receiving stable methadone maintenance therapy who were not infected with the human immunodeficiency virus. Intervention. Tenofovir DF was added to the subjects' methadone regimens. Measurements and Main Results. The pharmacokinetics of total, R‐, and S‐methadone were evaluated at baseline and after 2 weeks of daily tenofovir DF coadministration with a light meal. Steady‐state tenofovir DF pharmacokinetics were evaluated at day 15. Bioequivalence testing was conducted of total, R‐, and S‐methadone area under the serum or plasma concentration‐time curve during the 24‐hour dosing interval at steady state (AUC ss ) and maximum concentration in serum or plasma (C max ). Subjects were evaluated for changes in methadone pharmacodynamics by the Short Opiate Withdrawal Scale (SOWS) and pupillary diameter measurements at frequent intervals. Coadministration with tenofovir DF did not affect the pharmacokinetics of methadone. Geometric mean R‐methadone systemic exposures, AUC ss and C max , differed by 5% or less when methadone was dosed with tenofovir D F. Similar results were observed for S‐methadone and for total methadone. Both AUC ss and C max met the strict criteria for bioequivalence between the two study periods for total, R‐, and S‐methadone, indicating a lack of drug interaction when tenofovir DF was coadministered with methadone. No significant changes in SOWS scores or pupillary diameter measurements occurred, and no notable clinical adverse events were reported. Conclusion. Tenofovir DF pharmacokinetics were comparable to previously reported values of tenofovir DF in HIV‐infected patients. Coadministration of methadone with tenofovir DF did not alter the pharmacokinetics or pharmacodynamics of total, R‐, or S‐methadone. Tenofovir DF may be given as part of a once‐daily antiretroviral regimen in patients receiving methadone maintenance therapy.