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
References
Oct 1, 1991·Antimicrobial Agents and Chemotherapy·M Schäfer-KortingA Lukacs
Jan 1, 1989·Mycoses·J HeykantsG Cauwenbergh
Sep 1, 1988·Antimicrobial Agents and Chemotherapy·T C HardinJ G Kuhn
Nov 1, 1985·Antimicrobial Agents and Chemotherapy·M J HumphreyM H Tarbit
Jan 23, 1987·Journal of Chromatography·R WoestenborghsJ Heykants
Jul 1, 1988·The American Review of Respiratory Disease·M WillcoxT E King
Feb 1, 1986·Journal of Applied Physiology·S I RennardR G Crystal
Oct 1, 1993·Antimicrobial Agents and Chemotherapy·J S HostetlerD A Stevens
Apr 1, 1993·Antimicrobial Agents and Chemotherapy·J A BaroneV Van de Velde
Apr 1, 1993·Antimicrobial Agents and Chemotherapy·J R PerfectD T Durack
Sep 1, 1995·Infection·M Schäfer-KortingW Obermüller
May 1, 1996·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·C A Kauffman
Jul 1, 1996·Antimicrobial Agents and Chemotherapy·J E ConteE Zurlinden
Nov 1, 1996·Gastroenterology·G BarbaroG Di Lorenzo
Dec 13, 1996·Journal of Chromatography. B, Biomedical Applications·D CompasP N de Goede
Oct 31, 1998·Antimicrobial Agents and Chemotherapy·E K ManavathuP H Chandrasekar
Jan 13, 1999·Clinical Pharmacokinetics·J M Poirier, G Cheymol
Feb 13, 1999·Mayo Clinic Proceedings·C L Terrell
Mar 4, 1999·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·M S SaagW E Dismukes
Mar 4, 1999·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·R A Larsen
Sep 3, 1999·Antimicrobial Agents and Chemotherapy·D Andes, M van Ogtrop
Mar 7, 2000·The Journal of Antimicrobial Chemotherapy·F C Odds, H V Bossche
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·D Andes, M van Ogtrop
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·J E ConteE Zurlinden
Apr 1, 2000·Diagnostic Microbiology and Infectious Disease·D S BurgessM G Rinaldi
Oct 18, 2000·Diagnostic Microbiology and Infectious Disease·D S Burgess, R W Hastings
Jun 16, 2001·Antimicrobial Agents and Chemotherapy·G G ZhanelJ A Karlowsky
Sep 15, 2001·Antimicrobial Agents and Chemotherapy·J E ConteE Zurlinden
Dec 26, 2001·Antimicrobial Agents and Chemotherapy·L Joseph WheatRichard Hafner
Mar 19, 2002·Antimicrobial Agents and Chemotherapy·M A PfallerUNKNOWN SENTRY Participants Group
Apr 18, 2002·Antimicrobial Agents and Chemotherapy·Gloria M GonzálezJohn R Graybill
Apr 18, 2002·Antimicrobial Agents and Chemotherapy·John E ConteElisabeth Zurlinden
Jul 13, 2002·Cancer·Eric J BowStratis Ioannou
Jul 18, 2002·Antimicrobial Agents and Chemotherapy·John E ConteElisabeth Zurlinden
Feb 27, 2003·Antimicrobial Agents and Chemotherapy·M A PfallerR N Jones
Mar 26, 2003·Antimicrobial Agents and Chemotherapy·D AndesR Conklin
Apr 26, 2003·Acta Haematologica·D Caillot
May 6, 2003·The Journal of Antimicrobial Chemotherapy·Alasdair P MacGowan
May 20, 2003·Infectious Disease Clinics of North America·Robert W BradsherPeter G Pappas
Feb 1, 1965·Klinische Wochenschrift·H TALKE, G E SCHUBERT
Sep 25, 2003·Antimicrobial Agents and Chemotherapy·D AndesR Conklin
Dec 25, 2003·Antimicrobial Agents and Chemotherapy·D AndesDavid Loebenberg
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
Oct 19, 2011·Antimicrobial Agents and Chemotherapy·Pilar EscribanoJesús Guinea
Sep 21, 2011·Antimicrobial Agents and Chemotherapy·P CampoliD C Sheppard
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
May 12, 2010·Antimicrobial Agents and Chemotherapy·Fedja FarowskiCarsten Müller
May 5, 2010·Antimicrobial Agents and Chemotherapy·Thomas J WalshJohn E Conte
Dec 16, 2005·The AAPS Journal·Markus ZeitlingerChristian Joukhadar
Sep 15, 2009·Journal of Zoo and Wildlife Medicine : Official Publication of the American Association of Zoo Veterinarians·Elizabeth M BuntingGeorge V Kollias
Oct 7, 2011·Clinical Pharmacokinetics·Keith A RodvoldJomy M George
May 7, 2013·Expert Opinion on Drug Metabolism & Toxicology·Jodi Lestner, William W Hope
Feb 19, 2013·Toxicology and Applied Pharmacology·Yusheng QuHugo M Vargas
Sep 19, 2007·Revista iberoamericana de micología·José Ramón AzanzaBelén Sádaba
Mar 25, 2008·International Journal of Antimicrobial Agents·Yuko KanbayashiMasafumi Taniwaki
Apr 21, 2006·Microbiology and Immunology·Katsuyuki MakiSeitaro Mutoh
Apr 6, 2016·Frontiers in Microbiology·Peng ZhangZonghui Yuan
Oct 3, 2015·Mycoses·Roie TzadokJacob Strahilevitz
Dec 3, 2014·Revista iberoamericana de micología·José Ramón AzanzaAlmudena Gómez-Guíu
Jan 8, 2014·Clinical Microbiology Reviews·Timothy FeltonWilliam W Hope
Mar 1, 2019·Medical Mycology·Yanan ZhaoDavid S Perlin
Sep 18, 2014·Current Opinion in Infectious Diseases·Michael J Dolton, Andrew J McLachlan
Nov 7, 2019·British Journal of Clinical Pharmacology·David L HavaJames Roach
Dec 20, 2020·Pharmacology Research & Perspectives·Lindsey CassGarth Rapeport
Mar 23, 2021·EBioMedicine·Laurens LiesenborghsPeter Verhamme