Effect of coadministered ketoconazole, a strong cytochrome P450 3A4 enzyme inhibitor, on the pharmacokinetics of ciclesonide and its active metabolite desisobutyryl-ciclesonide.

Clinical Pharmacokinetics
Gabriele M BöhmerRüdiger Nave

Abstract

Cytochrome P450 (CYP) 3A4 isoenzyme has been identified in vitro as the key enzyme to metabolize desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of the inhaled corticosteroid ciclesonide. This pharmacokinetic drug-drug interaction study was conducted to confirm this major metabolic pathway in vivo by using the strong CYP3A4 inhibitor ketoconazole, and to assess the effect of ketoconazole on the pharmacokinetics of ciclesonide and des-CIC. Fourteen healthy adults participated in this open-label, nonrandomized, fixed sequence, two-period, repeated-dose pharmacokinetic study. During the first 7-day treatment period, the subjects orally inhaled ciclesonide 320 microg once daily. During the second 7-day treatment period, the subjects continued with the same dose of orally inhaled ciclesonide and concomitantly received oral ketoconazole 400 mg once daily. Pharmacokinetic profiles for ciclesonide and des-CIC were obtained on day 7 of each study period. For the parent compound, ciclesonide, no changes in the pharmacokinetic parameter estimates--the area under the serum concentration-time curve during the dosage interval (AUC(tau)), maximum serum concentration (C(max)) and time to reach the C(max)--were obse...Continue Reading

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Citations

Sep 13, 2012·European Journal of Clinical Pharmacology·Ines FuchsGerd Mikus
Jun 6, 2009·Clinical Pharmacokinetics·Rüdiger Nave
Feb 2, 2016·Journal of Clinical Pharmacology·Peymaan S BanankhahDavid J Greenblatt
Oct 22, 2011·Expert Review of Clinical Immunology·Robert L Jacobs
Oct 28, 2016·British Journal of Clinical Pharmacology·Sarah Talavera PonsArmand Abergel
Nov 30, 2018·Current Drug Metabolism·Panjasaram Naidoo, Manoranjenni Chetty
Jul 29, 2009·Archives of Biochemistry and Biophysics·Hugues OuelletPaul R Ortiz de Montellano

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