十一酸睾酮的应用及其药理作用

简介

十一酸睾酮为雄激素类药，为睾酮的十一酸酯，是睾酮的衍生物。可促进男性生长，男性第二性征和睾丸、副性腺结构的发育，促进蛋白质合成，使其减少分解，增强免疫功能，促进骨骼生长，促进红细胞生成，反馈性抑制促性腺激素分泌，抑制雌激素分泌[1-2]。十一酸睾酮的常用剂型为胶囊剂、丸剂、注射剂。为激素药。用于治疗原发性或继发性睾丸功能减退；男孩体质性青春期延迟；乳腺癌转移的姑息性治疗；再生障碍性贫血的辅助治疗；中老年部分性雄激素缺乏综合征[3-4]。其结构式如图1所示。

图1十一酸睾酮的结构式。

应用

十一酸睾酮用于治疗原发性或继发性睾丸功能减退；男孩体质性青春期延迟；乳腺癌转移的姑息性治疗；还可以用于男性原发性或继发性性腺功能低下的睾酮补充疗法，例如睾丸切除后；无睾症；垂体功能低下；内分泌性阳萎；由于精子生成障碍所引起的不育症；男性更年期症状，例如性欲减退，脑力和体力下降等[5-7]。此外，十一酸睾酮用于男子性腺功能低下症的睾酮替代疗法，如睾丸切除以后、类无睾症、垂体功能低下、内分泌性阳萎、男子更年期症状（性欲、脑力及体力减退等）、某些因生精功能失调而致的不育症以及再生障碍性贫血等[8-10]。

不良反应

十一酸睾酮作为雄激素治疗可能引起的不良反应如下：良性肿瘤、恶性肿瘤和非定性肿瘤（包括囊肿和息肉）：良性前列腺增生、前列腺癌。血液和淋巴系统疾患：红细胞增多症。代谢和营养紊乱：液体和盐潴留[11]。精神紊乱：抑郁、紧张感、情绪困扰、性欲增强、性欲减退。胃肠道紊乱：恶心、腹泻、腹部不适、腹痛。肝胆病症：淤胆型黄疸。皮肤和皮下组织疾患：瘙痒。肌（与）骨骼及结缔组织疾患：肌痛、骨骺早闭。血管疾患：高血压。肾和泌尿疾患：泌尿疾病[12]。生殖系统和乳腺疾患：男子乳房女性化、少精、无精子、阴茎持续勃起症、勃起频率增加、加速性成熟、阴茎增大。肝功能异常、血清前列腺特异性抗原（PSA）升高、血红蛋白升高、红细胞压积升高、血脂异常。

药代动力学

与睾酮不同，十一酸睾酮口服后具有活性是因为其一部分与乳糜微粒结合，被吸收并释放进入体循环淋巴液。在药物吸收过程中，少量十一酸睾酮代谢为同样具有活性的5α-十一酸双氢睾酮[13]。吸收后，残留的药物成分在肠壁和肝脏内代谢成无活性的生物转化产物。吸收进入淋巴液的酯类物质经水解，在外周循环中转化成雌二醇。之后，这些游离类固醇向靶器官发挥雄激素活性。在稳态条件下，单次给予本品80-160mg，4－5小时后血浆睾酮水平达到峰值，约为40nmol/l[14]。血浆睾酮水平可在服药后维持8－12小时。消除过程与天然睾酮相同，都是通过葡萄糖醛酸反应完成的。终产物主要经肾脏排泄，少部分经粪便排出。

毒理作用

小鼠皮下注射十一酸睾酮3.7g/kg（大鼠有效量的270倍），14天内未发现死亡或异常反应。大鼠肌内注射十一酸睾酮每天每公斤42mg，连续6个月，未见明显的肝肾功能改变或其他损害。

药物相互作用

十一酸睾酮与环孢素合用，环孢素毒性增强，引发肾脏损害、胆汁淤积、感觉异常等不良反应，应避免合用。十一酸睾酮与肾上腺皮质激素合用，可加重水肿。十一酸睾酮与口服抗凝药合用，出血的危险性增加[15]。十一酸睾酮与巴比妥类合用，可使本药代谢加快，疗效降低。十一酸睾酮与当归合用，抑制本药代谢，增加其雄激素效应和不良反应发生率。糖尿病患者应用本药，能够降低血糖，故应减少胰岛素的用量十一酸睾酮与紫杉醇合用，可抑制紫杉醇的代谢，导致毒性增强[16-17]。

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