STASS H, SCHUHLY U, DELESEN H, MOLLER J, NAGELSCHMITZ J; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 39.
Bayer AG, Wuppertal, Germany
BACKGROUND: MFX is neither metabolised by nor inhibits CYP 450 isozymes. This study served to confirm these results in vivo using ITR as a strong CYP 3A4 inhibitor.METHODS: 12 healthy male subjects received according to random plan 400 mg oral MFX alone or on the 7th day of an oral ITR 200 mg BID treatment over 9 days. Besides the assessment of safety and tolerability, non-compartmental PK of MFX, ITR and their metabolites were determined based on HPLC measurements.RESULTS: The treatments were well tolerated. Lack of an interaction was shown for MFX and its sulpho-metabolite (M1). For M2 (glucuronide) a 30% decrease in AUC was observed, accompanied by an approx. 54% increase in renal excretion, which may be due to phase II reactions and/or changes in transport mechanisms induced by ITR. Exposure (AUC) to ITR and its hydroxy-metabolite was only marginally altered by MFX (AUC +5% for ITR and -5% OH-ITR) indicating absence of a relevant influence of MFX on ITR. Cmax was reduced for both compounds by ap-proximately 14, 18%.CONCLUSIONS: For MFX involvement in interactions via CYP450 3A4 isozymes can be excluded confirming the in vitro results indicating absence of an inhibitory potential of MFX on this isozyme. MFX can be safely co-administered with oral ITR without considering dose adjustments.KEYWORDS: Interaction; Itraconazole; Moxifloxacin
Publication Types:
Keywords:
- Area Under Curve
- Aza Compounds
- Drug Interactions
- Humans
- In Vitro
- Itraconazole
- Male
- Quinolines
- moxifloxacin
- pharmacokinetics
Other ID:
UI: 102248609
From Meeting Abstracts