Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug

Abstract

The metabolism of a new synthetic progestagen, Org 2969 was studied in 4 healthy female volunteers. During the first part of the study (Phase I), the volunteers ingested 50 \g=m\g(about 0.1 mCi) of [16-3H]Org 2969 together with 50 \ g=m\ g of ethinyloestradiol as a single dose. During the second part of the study (Phase II), a 10-day pre-treatment with the same dosage of nonradioactive compound preceded the administration of the radioactive steroid.A peak level of total radioactivity, representing 3.16\p=n-\ 5.02% of the dose given/l of serum, was achieved within 2\p=n-\3 h in Phase I. During Phase II, the corresponding figures were 4.54\p=n-\5.13%after 1.5\p=n-\3 h. The difference was mainly due to an increase of freely-extractable steroids during Phase II. The difference can at least partly be explained by assuming a change in the kinetics of the metabolism of Org 2969 by pre-treatment with Org 2969 and ethinyloestradiol. The mean recovery of radioactivity in urine and faeces was 83.0%/48.1%/34.9% (total/ urine/faeces) of the total dose in Phase I and 76.1%/ 45.2%/30.9% during Phase II. The differences in the total excretion and in the radioactivity excreted in the faeces were significant.

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application

“…Desogestrel (DG) is the orally administered prodrug of ETO (3‐ketodesogestrel), which is rapidly absorbed and metabolized to ETO 52 . As a result, an oral PBPK model of DG with metabolism to ETO was developed.…”

“…Desogestrel (DG) is the orally administered prodrug of ETO (3-ketodesogestrel), which is rapidly absorbed and metabolized to ETO. 52 As a result, an oral PBPK model of DG with metabolism to ETO was developed. The DG model used the PE module along with observed oral clinical data to derive V ss and enzymatic intrinsic clearance (CL int ) for DG.…”

“…The DG model used the PE module along with observed oral clinical data to derive V ss and enzymatic intrinsic clearance (CL int ) for DG. 52 The specific metabolic route for DG metabolism to ETO is not fully known, hence a surrogate within Simcyp Simulator (CYP2J2) was used, with the PE predicted clearance, to allow metabolic conversion to ETO. The choice of CYP2J2 as a surrogate was based upon the enzyme abundance of only extensive metabolizer phenotype with interindividual variation, while it is acknowledged that the tissue distribution and interindividual variation may not well match the complete in vivo metabolic enzyme profile.…”

Motivos de retiro del implante subdérmico en el Hospital Escuela de Honduras, 2014 a 2015

“…Cada comprimido de la única minipíldora presente actualmente en nuestro país contiene 75 µg de desogestrel, un gestágeno muy selectivo con actividad androgénica débil (1). Tras la administración oral, el desogestrel se absorbe rápidamente y se transforma en su metabolito activo (2), etonogestrel, el cual es responsable de sus efectos hormonales. Etonogestrel es la denominación actual aceptada internacionalmente para el metabolito 3-ketodesogestrel.…”

Oral Progestogen Combined with Testosterone as a Potential Male Contraceptive: Additive Effects between Desogestrel and Testosterone Enanthate in Suppression of Spermatogenesis, Pituitary-Testicular Axis, and Lipid Metabolism1

“…ENG does not lower circulating HDL-C or apolipoprotein A1 when coadministered with estrogens in women (24). Based on the results of steady state studies and on excretion data, ENG (unlike MPA) does not accumulate in the body (25). Desogestrel (DSG), which is converted by the liver to ENG as the active metabolite, has been used widely in the combined oral female contraceptive (Marvelon, N.V. Organon, Oss, The Netherlands) since 1981.…”