Intrapulmonary pharmacokinetics and pharmacodynamics of itraconazole and 14-hydroxyitraconazole at steady state

Antimicrobial Agents and Chemotherapy
John E ConteElisabeth Zurlinden

Abstract

We determined the steady-state intrapulmonary pharmacokinetic and pharmacodynamic parameters of orally administered itraconazole (ITRA), 200 mg every 12 h (twice a day [b.i.d.]), on an empty stomach, for a total of 10 doses, in 26 healthy volunteers. Five subgroups each underwent standardized bronchoscopy and bronchoalveolar lavage (BAL) at 4, 8, 12, 16, and 24 h after administration of the last dose. ITRA and its main metabolite, 14-hydroxyitraconazole (OH-IT), were measured in plasma, BAL fluid, and alveolar cells (AC) using high-pressure liquid chromatography. Half-life and area under the concentration-time curves (AUC) in plasma, epithelial lining fluid (ELF), and AC were derived using noncompartmental analysis. ITRA and OH-IT maximum concentrations of drug (C(max)) (mean +/- standard deviation) in plasma, ELF, and AC were 2.1 +/- 0.8 and 3.3 +/- 1.0, 0.5 +/- 0.7 and 1.0 +/- 0.9, and 5.5 +/- 2.9 and 6.6 +/- 3.1 microg/ml, respectively. The ITRA and OH-IT AUC for plasma, ELF, and AC were 34.4 and 60.2, 7.4 and 18.9, and 101 and 134 microg. hr/ml. The ratio of the C(max) and the MIC at which 90% of the isolates were inhibited (MIC(90)), the AUC/MIC(90) ratio, and the percent dosing interval above MIC(90) for ITRA and OH-IT co...Continue Reading

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Citations

May 27, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Ilka SteinerMeinhard Kneussl
Sep 12, 2007·Antimicrobial Agents and Chemotherapy·Sungmin Kiem, Jerome J Schentag
May 23, 2007·Antimicrobial Agents and Chemotherapy·Susan M Abdel-RahmanJeffrey L Blumer
Nov 26, 2008·Antimicrobial Agents and Chemotherapy·John E ConteElisabeth Zurlinden
Aug 26, 2009·Antimicrobial Agents and Chemotherapy·Stefan WeilerRomuald Bellmann
Sep 23, 2009·Antimicrobial Agents and Chemotherapy·Jared L CrandonJoseph L Kuti
Dec 31, 2008·Antimicrobial Agents and Chemotherapy·Anthony M NicasioJoseph L Kuti
Jun 3, 2010·Antimicrobial Agents and Chemotherapy·John E ConteJeffrey A Golden
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Dec 20, 2020·Pharmacology Research & Perspectives·Lindsey CassGarth Rapeport

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