Pharmacokinetics of oestrone-3-Ο-sulphamate

M. I. Hidalgo Aragones, A. Purohit, D. Parish, U. G. Sahm, C. W. Pouton, B. V.L. Potter, M. J. Reed

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Abstract

The sulphatase pathway is thought to be the major route of oestrogen synthesis in breast tumours in postmenopausal women. There is currently considerable interest in developing a potent steroid sulphatase inhibitor to block oestrogen synthesis by this route. One of the most potent inhibitors discovered so far is oeslirone-3-Ο-sulphamate (EMATE) which is active in vivo. In this study we report the preparation of a formulation for the administration of EMATE by the oral route. A method, using high-performance liquid chromatography (HPLC), was also established to measure concentrations of EMATE in rat plasma after its oral or i.v. administration. Using the oral formulation and HPLC assay, EMATE was readily detected in rat plasma after oral administration. Plasma EMATE concentrations were related to the dose of drug administered orally over the 10-40 mg/kg range. To examine the pharmacokinetics of EMATE, the compound (40 mg/kg, single dose) was administered either orally (in the formulation) or i.v. (in propylene glycol) with plasma samples being collected for up to 6 h. After oral administration, EMATE was rapidly absorbed, with the peak plasma concentration being detected at 30 min, after which plasma concentrations rapidly decreased. After i.v. administration a plasma EMATE concentration was detected at 1 h similar to that after oral administration. The clearance of EMATE from plasma followed a bi-phasic curve, showing an initial half-life of 30 min, followed by a slower half-life of 4 h 30 min. Little evidence was obtained for any metabolism of EMATE to oestrone. Rat liver sulphatase activity was almost completely inhibited (>99%) within 30 min of oral or i.v. administration of EMATE.

Original languageEnglish
Pages (from-to)611-617
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume58
Issue number5-6
Publication statusPublished - 1 Jan 1996

Cite this

Hidalgo Aragones, M. I., Purohit, A., Parish, D., Sahm, U. G., Pouton, C. W., Potter, B. V. L., & Reed, M. J. (1996). Pharmacokinetics of oestrone-3-Ο-sulphamate. Journal of Steroid Biochemistry and Molecular Biology, 58(5-6), 611-617.
Hidalgo Aragones, M. I. ; Purohit, A. ; Parish, D. ; Sahm, U. G. ; Pouton, C. W. ; Potter, B. V.L. ; Reed, M. J. / Pharmacokinetics of oestrone-3-Ο-sulphamate. In: Journal of Steroid Biochemistry and Molecular Biology. 1996 ; Vol. 58, No. 5-6. pp. 611-617.
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Hidalgo Aragones, MI, Purohit, A, Parish, D, Sahm, UG, Pouton, CW, Potter, BVL & Reed, MJ 1996, 'Pharmacokinetics of oestrone-3-Ο-sulphamate', Journal of Steroid Biochemistry and Molecular Biology, vol. 58, no. 5-6, pp. 611-617.

Pharmacokinetics of oestrone-3-Ο-sulphamate. / Hidalgo Aragones, M. I.; Purohit, A.; Parish, D.; Sahm, U. G.; Pouton, C. W.; Potter, B. V.L.; Reed, M. J.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 58, No. 5-6, 01.01.1996, p. 611-617.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hidalgo Aragones, M. I.

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Hidalgo Aragones MI, Purohit A, Parish D, Sahm UG, Pouton CW, Potter BVL et al. Pharmacokinetics of oestrone-3-Ο-sulphamate. Journal of Steroid Biochemistry and Molecular Biology. 1996 Jan 1;58(5-6):611-617.