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Metabolism of Gestobutanoil, a Novel Drug of Progestin Group

Metabolism of Gestobutanoil, a Novel Drug of Progestin Group

Stepanova E.S., Makarenkova L.M., Chistyakov V.V., Fedotcheva T.A., Parshin V.A., Shimanovsky N.L.
Key words: metabolism; pharmacokinetics; gestagens; Gestobutanoil; HPLC-MS; steroids.
2019, volume 11, issue 3, page 48.

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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.

  1. Sergeyev P.V., Fedotcheva T.A., Rzheznikov V.M., Grinenko G.S., Semeykin A.V., Vetchinkina V.B., Atroshkin K.A., Shimanovsky N.L. A new russian gestagen with anticancer activity. Vestnik Rossiiskoi akademii meditsinskikh nauk 2007; 5: 27–32.
  2. Sergeev P.V., Rzheznikov V.M., Korkhov V.V., Grinenko G.S., Semeikin A.V., Mayatskaya E.E., Shimanovskii N.L. Investigation of the gestagen activity of 17α-acetoxy-3β-butanoyloxy-6-methylpregna-4,6-dien-20-one. Khimiko-farmatsevticheskii zhurnal 2005; 39(7): 2005; 39(7): 20–22.
  3. Sheina N.I., Parshin V.A., Rybakov Yu.L., Gukasov V.M., Kostyaeva M.G., Semeikin A.V., Samoilikov R.V., Fedotcheva T.A., Shimanovskii N.L. Evaluation of the toxicity of new progestogen gestobutanoil in experiments on rats and mice. Eksperimental’naya i klinicheskaya farmakologiya 2018; 81(11): 18–25.
  4. Rukovodstvo po ekspertize lekarstvennykh sredstv. T. I [Guidelines for the examination of medicines. V. I]. Moscow: Grif i K; 2013.
  5. Stepanova E.S., Makarenkova L.M., Chistyakov V.V., Rybakov Y.L., Gukasov V.M., Fedotcheva T.A., Parshin V.A., Votyakov V.A., Shimanovskii N.L. HPLC-MS method for simultaneous quantification of innovative steroid drug and its metabolites in the blood sera of rats and rabbits. Khimiko-farmatsevticheskii zhurnal 2018; 52(12): 75–79,
  6. Jordan A. Toxicology of depot medroxyprogesterone acetate. Contraception 1994; 49(3): 189–201,
  7. Schindler A.E., Campagnoli C., Druckmann R., Huber J., Pasqualini J.R., Schweppe K.W., Thijssen J.H. Classification and pharmacology of progestins. Maturitas 2003; 46(Suppl 1): S7–S16,
  8. Chen J., Zhang J.-W., Yang L., Li W. Structure elucidation of major metabolites from medroxyprogesterone acetate by P450. Chem Pharm Bull 2009; 57(8): 835–839,
  9. Sturm G., Häberlein H., Bauer T., Plaum T., Stalker D.J. Mass spectrometric and high-performance liquid chromatographic studies of medroxyprogesterone acetate metabolites in human plasma. J Chromatogr 1991; 562(1–2): 351–362,
  10. Zeinalov O.A., Yaderets V.V., Stytsenko T.S., Petrosyan M.A., Andryushina V.A. Synthesis and biological activity of synthetic 17α-hydroxyprogesterone derivatives. Khimiko-farmatsevticheskii zhurnal 2012; 46(4): 7–10.
Stepanova E.S., Makarenkova L.M., Chistyakov V.V., Fedotcheva T.A., Parshin V.A., Shimanovsky N.L. Metabolism of Gestobutanoil, a Novel Drug of Progestin Group. Sovremennye tehnologii v medicine 2019; 11(3): 48,

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