Effects of TAP-144-SR, A Sustained-Release Formulation of a Potent GnRH Agonist, on Experimental Endometriosis in the Rat.

Sudo K, K Sudo, Katsuichi Sudo, Shiota K, K. Shiota, Kunio Shiota, Tsuneo Masaki, Masaki T, T Masaki, T Fujita, Fujita T, Takeshi Fujita
Endocrinologia japonica · 1991 · vol. 38(1) , pp. 39–45 · doi:10.1507/endocrj1954.38.39 · PMID:1915112 · W2001553142
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TAP-144-SR, a sustained-release GnRH agonist, suppressed experimental endometriosis growth and reduced hormone levels in rats, showing greater efficacy than TAP-144 solution.

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Researchers established a novel rat model by auto-transplanting endometrial tissue beneath kidney capsules to evaluate the efficacy of TAP-144-SR, a sustained-release formulation of the GnRH agonist leuprolide. The study demonstrated that single subcutaneous injections of this microcapsule formulation suppressed the growth of transplanted endometrial tissues and uterine weight in a dose-dependent manner, with effects comparable to ovariectomy at higher doses. This suppression was more pronounced than that achieved with standard TAP-144 solution, which also resulted in greater reductions in serum and pituitary levels of LH and FSH. The paper is centrally about endometriosis — specifically utilizing an experimental animal model to assess the therapeutic potential of a sustained-release GnRH agonist for treating the condition.

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Abstract

A new, simple experimental endometriosis model was established by auto-transplanting endometrial tissue fragments beneath kidney capsules in female rats. The transplanted endometrial tissue grew well, forming a fluid-filled cyst, which reached maximal size 2 to 3 weeks after transplantation. The growth and maintenance of the transplants was dependent on the ovary: ovariectomy induced regression of well grown transplants. The therapeutic effects of TAP-144-SR (biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model. A single sc injection of TAP-144-SR (corresponding to 1, 10 or 100 micrograms/kg/day of TAP-144), suppressed the growth of the transplanted endometrial tissues and uterine weight in a dose-dependent manner. At 100 micrograms/kg/day, the suppressive effect was more marked in rats given TAP-144-SR than in those given TAP-144 solution. The extent of suppression was comparable to that caused by ovariectomy. Serum and pituitary concentrations of LH and FSH were also reduced more markedly by the administration of TAP-144-SR than by TAP-144 solution. From these results, the present endometriosis model was found to be useful for the evaluation of compounds with potential therapeutic activity. The sustained-release formulation of TAP-144 seems to be beneficial over its solution in terms of both convenience and efficiency for therapy of patients with endometriosis.
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Effects of TAP-144-SR, A Sustained-Release Formulation of a Potent GnRH Agonist, on Experimental Endometriosis in the Rat 1991 Volume 38 Issue 1 Pages 39-45 Details Abstract A new, simple experimental endometriosis model was established by auto-transplanting endometrial tissue fragments beneath kidney capsules in female rats. The transplanted endometrial tissue grew well, forming a fluid-filled cyst, which reached maximal size 2 to 3 weeks after transplantation. The growth and maintenance of the transplants was dependent on the ovary: ovariectomy induced regression of well grown transplants. The therapeutic effects of TAP-144-SR biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model. A single sc injection of TAP-144-SR (corresponding to 1, 10 or 100μg/kg/day of TAP-144), suppressed the growth of the transplanted endometrial tissues and uterine weight in a dose-dependent manner. At 100μg/kg/day, the suppressive effect was more marked in rats given TAP-144-SR than in those given TAP-144 solution. The extent of suppression was comparable to that caused by ovariectomy. Serum and pituitary concentrations of LH and FSH were also reduced more markedly by the administration of TAP-144-SR than by TAP-144 solution. From these results, the present endometriosis model was found to be useful for the evaluation of compounds with potential therapeutic activity. The sustained-release formulation of TAP-144 seems to be beneficial over its solution in terms of both convenience and efficiency for therapy of patients with endometriosis. © The Japan Endocrine Society Favorites & Alerts Recently viewed articles Successor

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Leuprolide Uterine Neoplasms Animals Antineoplastic Agents Antineoplastic Agents Delayed-Action Preparations Disease Models, Animal Dose-Response Relationship, Drug Endometriosis Endometrium Endometrium Endometrium Female Follicle Stimulating Hormone Follicle Stimulating Hormone Leuprolide Luteinizing Hormone Luteinizing Hormone Organ Size

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