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Pharmacokinetic interaction between voriconazole and methadone at steady state in methadone patients
Author(s) -
Liu P.,
Foster G.,
Labadie R.,
Somoza E.,
Sharma A.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.014
Subject(s) - meth , cmax , pharmacokinetics , methadone , pharmacology , voriconazole , medicine , placebo , anesthesia , chemistry , antifungal , alternative medicine , monomer , organic chemistry , pathology , dermatology , acrylate , polymer
Aim Voriconazole (VORI), a triazole antifungal agent, is metabolized by the cytochrome P450 CYP2C19, CYP2C9 and to a lesser extent by CYP3A4. Methadone (METH), a μ‐opioid receptor agonist, is primarily metabolized by the CYP3A4. This study was conducted to evaluate the pharmacokinetic (PK) interactions between these two compounds. Methods A randomized, subject and investigator blinded, placebo controlled, parallel group multiple dose study was conducted in 23 male methadone patients. Subjects continued to receive individualized maintenance dose of METH alone (30–100 mg QD) for 2 days after entering the study. Therapeutic dose of VORI (400 mg BID on day 1 followed by 200 mg BID) or placebo were co‐administered for the next 5 days. The steady state PK of VORI and METH following 5 days of co‐administration (Day 7) were compared to those of METH alone (Day 2) and VORI alone in a reference study (conducted in 34 healthy subjects). Results VORI increased the daily mean steady state area under the concentration‐time curve (AUC 0–24 ) of pharmacologically active enantiomer R‐METH by 47.20% (90% CI: 37.65–57.41%), and peak concentration (C max ) of R‐METH by 30.69% (90% CI: 22.17–39.81%). The magnitude of increase in S‐METH exposure was greater than that of R‐METH (AUC 0–24 : 103.36%; C max : 65.39%). METH appeared to have no effect on the steady state VORI PK. Conclusions Caution should be exercised with METH due to the moderate increase in R‐METH exposure by VORI. Clinical Pharmacology & Therapeutics (2005) 77 , P32–P32; doi: 10.1016/j.clpt.2004.12.014