Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. Pharmacokinetics after an oral dose

Viinikka, Lasse; Ylikorkala, Olavi; Vihko, R.; Wijnand, Herman P.; Booij, M.; Veen, F. van der

doi:10.1007/bf00558439

Cited by 33 publications

(15 citation statements)

References 9 publications

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“…The pharmacokinetic profile of desogestrel and its metabolite etonogestrel (or 3-ketodesogestrel) has been described in numerous research articles using young healthy volunteers [6–9]. In receptor binding studies, a greater affinity of the metabolite (3-ketodesogestrel) for the human progesterone receptor, compared to parent drug (desogestrel), has been shown.…”

Section: Introductionmentioning

confidence: 99%

Randomized, Crossover and Single-Dose Bioequivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 µg) in Healthy Female Volunteers

Pena

Sanz²,

Francisco³

et al. 2012

Sci. Pharm.

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Despite the increase in the substitution of branded medicinal product with generic drugs, this is a controversial issue for some pharmacological groups (such as contraceptives).The aim of the present clinical trial was to assess the bioequivalence and tolerability of two oral formulations of desogestrel.Thirty-three healthy female volunteers participated in this randomized and two-way crossover study. During two separate experimental periods, with at least four weeks of washout period, women received a single oral dose of 75 μg of desogestrel from each of the formulations (test formulation and reference formulation). Desogestrel bioavailability was determined by the measurement of 3-ketodesogestrel plasma concentration.Pharmacokinetic parameters were comparable and the 90% CI for the ratio of Cmax (96.14–114.53%) and AUC0–t (105.73–123.83%) values for the test and reference formulations fell within the established regulatory interval (80–125%). Both formulations were also comparable in terms of tolerability.From the results of this study it can be concluded that test formulation (desogestrel 75 μg, Cyndea PHARMA S.L.) is bioequivalent to the reference formulation (Cerazet® 75 μg, Organon Española S.A.).

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Section: Introductionmentioning

confidence: 99%

Randomized, Crossover and Single-Dose Bioequivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 µg) in Healthy Female Volunteers

Pena

Sanz²,

Francisco³

et al. 2012

Sci. Pharm.

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“…This, in turn, may indicate a change in the kinetics of Org 2969 during pre-treatment with the progestagen-ethinyloestradiol combination. This may be due to a reduced apparent volume of distribution of the main metabolite of Org 2969, 3-keto-Org 2969, and/or and increase in the frac¬ tion of Org 2969 which is metabolized to 3-ketoOrg 2969 (Viinikka 1978(Viinikka , 1979Viinikka et al 1979). A reason for the decreased apparent vo¬ lume of distribution could be a change in protein binding.…”

Section: Discussionmentioning

confidence: 90%

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

Viinikka

Ylikorkala

Vihko

et al. 1980

Acta Endocrinologica

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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.

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“…The conversion of desogestrel to the active metabolite is fairly rapid in vivo (Viinikka et al, 1979;Hasenack et al, 1986; although in the study it was shown that the mean (± s.d.) bioavailability of 3-keto desogestrel was 76 ± 22% after oral administration of desogestrel to volunteers who also received intravenous 3-keto desogestrel.…”

Section: Introductionmentioning

confidence: 84%

Metabolism of the contraceptive steroid desogestrel by the intestinal mucosa.

Madden

Back

et al. 1989

Brit J Clinical Pharma

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1 The intestinal mucosal metabolism of the progestogen oral contraceptive desogestrel (Dg) has been studied in vitro using the Ussing chamber technique. Histologically normal ileum or colon was obtained from eight patients undergoing various resections. The mucosal sheets were mounted between two perspex chambers. 2 Two hours after addition of [3H]-Dg (0.2pXCi; 100 ng) to the mucosal chamber, more than 90% of the steroid was present in that chamber. In studies with colon, metabolite analysis showed that 55.4 ± 11.7% (mean ± s.d.; n = 6) of drug present was Dg, 28.9 + 11.4% as unconjugated Phase I metabolites, 13.3 ± 2.6% as sulphate conjugates and 2.5 + 1.5% as glucuronide conjugates. 3 By co-chromatography with authentic metabolites and mass spectrometry, it was shown that 3-keto desogestrel is formed in the mucosa. This is the active metabolite of desogestrel. A large peak of radioactivity did not co-chromatograph with any known metabolites and has been tentatively identified as ring hydroxylated products of 3-keto desogestrel. 4 The effect of the synthetic oestrogen ethinyloestradiol (EE2) on the metabolite profile of Dg was studied. In the presence of increasing concentrations of EE2 (100 ng, 1 and 10 ,ug), there was competition for sulphation such that the sulphate fraction decreased by 32, 49 and 48% respectively. 5 The results of this study indicate substantial first pass metabolism of desogestrel by the gut mucosa with evidence for the formation of the active metabolite. The extent of phase I metabolism is unusual.

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Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. Pharmacokinetics after an oral dose

Cited by 33 publications

References 9 publications

Randomized, Crossover and Single-Dose Bioequivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 µg) in Healthy Female Volunteers

Randomized, Crossover and Single-Dose Bioequivalence Study of Two Oral Desogestrel Formulations (Film-Coated Tablets of 75 µg) in Healthy Female Volunteers

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

Metabolism of the contraceptive steroid desogestrel by the intestinal mucosa.

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