Metabolism of gestobutanoil, a novel drug of progestin group

The aim of the study is to evaluate the metabolism of progestin drug Gestobutanoil in the experiment with administration of tablet dosage form containing Gestobutanoil (2 mg), to experimental animals (rats and rabbits). Materials and Methods. There was performed analysis of biomatrix obtained from different species of animals: female rats weighing 200.0±60.0 g and female rabbits weighing 3.0±0.2 kg, which were administered different doses of the drug, single or multiple. Metabolites were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). Results. The analysis shows that Gestobutanoil is rapidly metabolized into 17α-acetoxy-3β-hydroxy-6-methylpregna-4,6-dien-20-one (AMP-17) and 17-hydroxy-6-methylpregna-1,4-diene-3,20-dione in the form of acetate (MA). The steroid core of Gestobutanoil has the butyric acid radical in the 3β position. This radical cleavage underlies biotransformation of Gestobutanoil. The obtained pharmacokinetic parameters for metabolites have demonstrated that Gestobutanoil has a stepwise nature of metabolism: the time to reach the maximum concentration of AMP-17 is 1.5 h, MA — 3 h. Also AMP-17 proves to penetrate into the peripheral tissues better than MA. Conclusion. The data obtained speak of a unique, different from other gestagens, metabolism of Gestobutanoil. Unlike the known progestogen medroxyprogesterone acetate whose main route of transformation is hydroxylation of the steroid nucleus of the molecule with rather high bioavailability in an unchanged state, Gestobutanoil shows rapid biotransformation into metabolites AMP-17 and MA manifesting their own gestagenic activity with release of butyric acid, which, in turn, may produce a calming effect on the central nervous system. © 2019, Privolzhsky Research Medical University. All rights reserved.

Authors
Stepanova E.S. 1 , Makarenkova L.M. 1 , Chistyakov V.V. 2 , Fedotcheva T.A.3, 4 , Parshin V.A.3 , Shimanovsky N.L.5
Publisher
Nizhny Novgorod State Medical Academy
Number of issue
3
Language
English
Pages
48-53
Status
Published
Volume
11
Year
2019
Organizations
  • 1 Bioanalytical Mass Spectrometry Laboratory, Center for Collective Use (Scientific Educational Center), Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
  • 2 Center for Collective Use (Scientific Educational Center), Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
  • 3 Research Laboratory of Molecular Pharmacology, Pirogov Russian National Research Medical University, 1 Ostrovitianov St, Moscow, 117997, Russian Federation
  • 4 Metabolomics Laboratory, All-Russian Research Institute of Medicinal and Aromatic Plants, 7 Grin St, Moscow, 117216, Russian Federation
  • 5 Russian Academy of Sciences, Department of Molecular Pharmacology, Radiobiology named after Academician P.V. Sergeev, Pirogov Russian National Research Medical University, 1 Ostrovitianov St, Moscow, 117997, Russian Federation
Keywords
Gestagens; Gestobutanoil; HPLC-MS; Metabolism; Pharmacokinetics; Steroids
Date of creation
24.12.2019
Date of change
24.12.2019
Short link
https://repository.rudn.ru/en/records/article/record/55484/
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