Dijkman G A, del Moral P F, Plasman J W, Kums J J, Delaere K P, Debruyne F M, Hutchinson F J, Furr B J
Department of Urology, St Ignatius Hospital, Breda, The Netherlands.
J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):933-6. doi: 10.1016/0960-0760(90)90446-r.
A new depot formulation of the LHRH analogue Zoladex (goserelin acetate) has been developed which releases the drug over a period of at least 3 months as judged by measurement of drug content in depots at intervals after insertion in male rats and by the suppression of oestrogen secretion and oestrus in female rats. This formulation is based on the lactide/glycolide polymer system used for the standard 1-month Zoladex depot, but the dose has been increased to 10.8 mg and the characteristics have been modified to enable a longer release of drug to be achieved. Thirty-eight patients with histologically proven, locally advanced (stage T3 or T4) and/or metastatic prostate cancer were treated with this new longer acting LHRH analogue depot formulation containing 10.8 mg Zoladex. After initial increase of serum testosterone in the first week of therapy, castration levels were reached in all patients after 4 weeks and this was maintained for more than 14 weeks. At the time of depot exhaustion, when escape from castration levels of androgen occurred, all patients received a single injection of a standard 1-month depot containing 3.6 mg Zoladex which restored castration levels of androgen thus showing that the pituitary gland was again suppressed. The tolerance and acceptability of the longer-acting depot is high and comparable to the 1-month depot. Taking into account social and psychological factors, patients with advanced prostate carcinoma will soon be able to be treated with a longer acting LHRH depot formulation every 3 months an alternative of the 1-month depot now widely used clinically.
已研发出一种促黄体生成素释放激素（LHRH）类似物——诺雷德（戈舍瑞林醋酸盐）的新型长效注射剂。通过在雄性大鼠体内植入后定期测量注射剂中的药物含量，以及观察对雌性大鼠雌激素分泌和发情期的抑制作用判断，该注射剂可在至少3个月的时间内持续释放药物。此制剂基于用于标准1个月诺雷德长效注射剂的丙交酯/乙交酯聚合物系统，但剂量已增至10.8 mg，其特性也经过改良，从而能够实现更长时间的药物释放。38例经组织学证实为局部晚期（T3或T4期）和/或转移性前列腺癌的患者，接受了这种含10.8 mg诺雷德的新型长效LHRH类似物注射剂治疗。治疗第一周血清睾酮水平初步升高后，所有患者在4周后达到去势水平，并维持了超过14周。在长效注射剂药效耗尽、雄激素水平脱离去势水平时，所有患者均接受了一次含3.6 mg诺雷德的标准1个月长效注射剂注射，雄激素去势水平得以恢复，这表明垂体再次受到抑制。长效注射剂的耐受性和可接受性良好，与1个月长效注射剂相当。综合社会和心理因素考虑，晚期前列腺癌患者很快将能够每3个月接受一次长效LHRH注射剂治疗，作为目前临床上广泛使用的1个月长效注射剂的替代方案。
