The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after administration of desogestrel

Br J Clin Pharmacol. 2005 Jul;60(1):69-75. doi: 10.1111/j.1365-2125.2005.02382.x.


Aims: Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3-keto-desogestrel after administration of desogestrel, by using the selective inhibitors fluconazole (CYP2C) and itraconazole (CYP3A4).

Methods: This study had a three-way crossover design and included 12 healthy females, the data from 11 of whom were analyzed. In the first (control) phase all subjects received a single 150 microg oral dose of desogestrel alone. In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a randomized balanced order. Desogestrel was given 1 h after the last dose of the CYP inhibitor. Plasma 3-keto-desogestrel concentrations were determined for up to 72 h post dose.

Results: Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration-time curve (AUC) of 3-keto-desogestrel by 72.4% (95% confidence interval on the difference 12%, 133%; P = 0.024) compared with the control phase, whereas fluconazole pretreatment had no significant effect (95% CI on the difference -42%, 34%). Neither enzyme inhibitor affected significantly the maximum concentration (95% CI on the difference 14%, 124% for itraconazole and -23%, 40% for fluconazole) or elimination half-life (95% CI on the difference -42%, 120% for itraconazole and -24%, 61% for fluconazole) of 3-keto-desogestrel.

Conclusions: According to the present study, the biotransformation of desogestrel to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier. However, the further metabolism of 3-keto-desogestrel seems to be catalyzed by CYP3A4.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / physiology*
  • Contraceptives, Oral, Synthetic / administration & dosage
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / physiology*
  • Desogestrel / administration & dosage
  • Desogestrel / metabolism
  • Desogestrel / pharmacology*
  • Female
  • Genotype
  • Humans
  • Oxidoreductases, N-Demethylating / physiology*


  • Contraceptives, Oral, Synthetic
  • cytochrome P-450 CYP2C subfamily
  • etonogestrel
  • Desogestrel
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating