GHAHRAMANI P, PURKINS L, LOVE ER, EVE MD, FIELDING A, NICHOLS DJ; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 24.
Pfizer Central Res., Sandwich, United Kingdom
Objectives: To determine the effect of phenytoin (PH) on voriconazole (V) pharmacokinetics (study A) and to determine the effect of V on PH pharmacokinetics (study B).METHODS: Two placebo (PL)-controlled, randomized, parallel group studies were conducted in healthy men (aged 18-45y). Study A: In this open study all subjects (planned n=24) received V (400 mg bid Day 1, 200 mg bid Days 1-7 and 8-14 , 400 mg bid Days 22-28). Twelve subjects received PH (300 mg od) on Days 8-28, and 12 received PL on Days 8-21 and discharged. Study B: All subjects (planned n=24) received PH (a loading dose on Day 1, 300 mg od on Days 2-17). Subjects were randomized to receive V (400 mg bid) or PL on Days 8-17. Changes in maximum plasma concentration (C[max]), the area under plasma concentration-time curve within a dosing interval (AUCt ) and time to occurrence of C[max] (T[max]) were compared on Days 21 and 28 vs Day 7 (Study A) and Days 7 and 17 (Study B).RESULTS: Study A: 21 subjects were evaluable (10 V+PH, 11 V+PL). PH decreased the C[max] and AUCt of V but had no significant effect on T[max] (table). Parameters approached baseline (Day 7) levels on Day 28 (i.e., after increasing the dose of V to 400 mg bid). Study B: 15 subjects were evaluable (6 PH+V, 9 PH+PL). V increased C[max] and AUCt of PH but had no significant effect on T[max] [table: see text].CONCLUSIONS: PH decreases the plasma concentration of V. Increasing the V dose from 200 to 400 mg bid compensates for the observed decrease in C[max] and AUCt of V when co-administered with PH. V increased the C[max] and AUCt of PH. The plasma concentrations of PH should be monitored, and PH dose adjusted as appropriate, when coadministered with V.KEYWORDS: Interaction; Phenytoin; Voriconazole
Publication Types:
Keywords:
- Carrier Proteins
- Chromosomes
- DNA-Binding Proteins
- Drug Interactions
- Humans
- Hydrogen-Ion Concentration
- Male
- Phenytoin
- Pyrimidines
- Transcription Factors
- Triazoles
- genetics
- voriconazole
Other ID:
UI: 102248537
From Meeting Abstracts