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The Effects of Once‐Daily Saquinavir/Minidose Ritonavir on the Pharmacokinetics of Methadone
Author(s) -
Shelton Mark J.,
Cloen Denise,
DiFrancesco Robin,
Berenson Charles S.,
Esch Andrew,
Caprariis Pascal J.,
Palic Branka,
Schur Jane L.,
Buggé Christopher J. L.,
Ljungqvist Anders,
Espinosa Orlando,
Hewitt Ross G.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270003262956
Subject(s) - methadone , pharmacokinetics , saquinavir , ritonavir , medicine , dosing , pharmacology , anesthesia , concomitant , human immunodeficiency virus (hiv) , antiretroviral therapy , family medicine , viral load
Twelve methadone‐maintained HIV‐negative subjects were given saquinavir/ritonavir (SQV/rtv) 1600 mg/100 mg once daily for 14 days. Pharmacokinetic evaluations of total and unbound methadone enantiomers (R and S) were conducted before and after SQV/rtv. SQV/rtv was well tolerated, with no ACTG Grade 3–4 adverse events, no evidence of sedation, and no changes in methadone dose. For R‐methadone (active isomer), C max , AUC 0–24 h , and C min were unchanged, but percent unbound 4 hours after dosing was reduced by 12%. For S‐methadone, no differences in pharmacokinetic parameters of total drug were seen, but unbound concentrations were reduced by 15% and 21% at 4 and 24 hours after dosing, respectively. SQV trough concentrations exceeded the anticipated EC 50 (50 ng/mL) in 10/12 subjects, persisting for at least 6 hours after the final dose in 4/6 subjects. Once‐daily SQV/rtv in methadone‐maintained subjects is safe and not associated with any clinically significant interaction with methadone during 14 days of concomitant administration.