Deslorelin acetate, marketed under the trade names Ovuplant, SucroMate and Suprelorin, is an injectable gonadotropin releasing hormone super agonist (GnRH agonist), also known as a LHRH agonist. It prevents the production of sex hormones (testosterone and estrogen), controls the down-regulation of LH and FSH levels by stimulating a related surge in LH secretion, and then inhibits ovarian and testicular steroid biosynthesis, which can be used to treat advanced prostate cancer. Its amino acid sequence is Pyr-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-NHEt.
Large testosterone levels are a major factor in promoting the growth of prostate tumors, so it is necessary to reduce circulating testosterone to a very low (castration) level to achieve the effect of treating advanced prostate cancer. Deslorelin is mainly used for the initial glare effect on the pituitary gland, which will inhibit the transient secretion of luteinizing hormone (LH), thereby regulating the secretion of LH by negative feedback. Continuous administration of deslorelin leads to down-regulation of LH and follicle stimulating hormone (FSH). When testosterone levels in the blood decrease and testosterone-stimulated cancer stops dividing, the number of patients with advanced symptomatic prostate cancer will reduce.
Deslorelin acetate can reduce the mortality rate of patients with localized prostate cancer by one third. Deslorelin acetate is considered to be a new method for endocrine therapy of prostate cancer because of its good tolerance. Preliminary results from a multicenter phase III trial showed that deslorelin reduced tumor onset and morbidity in patients with D 2 stage prostate cancer. The average serum testosterone level of the first 22 patients in the trial after 7 days of treatment was 329.8 ng / dl. In contrast, testosterone levels in patients treated with leuprolide or goserelin for 7 days were 482.2 and 770.4 ng / dl, respectively. A significant reduction in mean serum testosterone levels (relative to baseline) was observed only in the deslorelin receptor. In contrast, patients treated with leuprolide or goserelin observed a significant increase.
Pharmacokinetics and Metabolism
Deslorelin has been evaluated by continuous subcutaneous injection. After administration of 9 healthy male volunteers by SC injection at 1 or 10 μg/kg, the plasma concentration of deslorelin was dose-dependent within 24 hours. The apparent volume of distribution increases with increasing plasma concentration. 12% of the administered dose was bound by plasma proteins. Deslorelin is a polypeptide amino acid whose metabolites are formed by hydrolysis of peptide bonds and have no significant oxidative or conjugated metabolites.
1. Hanks GE, Lu J, Machtay M. A phase III trial of the use of long term androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate. Proc 36th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, 2000, p128 -4112.
2. Roberts Pharmaceutical Corporation. Deslorelin(R): investigator's brochure [company communication]. Roberts Pharmaceutical Corporation; 1990, 64.
3. Harning R, Mailiard JA, Rospond R, et al. Deslorelin (a new LHRH agonist) significantly reduces tumor flare during early treatment of stage D2 prostate cancer[J]. 84th Annual Meeting of the American Association for Cancer Research; 1993,202(34), 19–22.