簡(jiǎn)介

十一酸睪酮為雄激素類藥，為睪酮的十一酸酯，是睪酮的衍生物?？纱龠M(jìn)男性生長(zhǎng)，男性第二性征和睪丸、副性腺結(jié)構(gòu)的發(fā)育，促進(jìn)蛋白質(zhì)合成，使其減少分解，增強(qiáng)免疫功能，促進(jìn)骨骼生長(zhǎng)，促進(jìn)紅細(xì)胞生成，反饋性抑制促性腺激素分泌，抑制雌激素分泌[1-2]。十一酸睪酮的常用劑型為膠囊劑、丸劑、注射劑。為激素藥。用于治療原發(fā)性或繼發(fā)性睪丸功能減退；男孩體質(zhì)性青春期延遲；乳腺癌轉(zhuǎn)移的姑息性治療；再生障礙性貧血的輔助治療；中老年部分性雄激素缺乏綜合征[3-4]。其結(jié)構(gòu)式如圖1所示。

圖1十一酸睪酮的結(jié)構(gòu)式。

應(yīng)用

十一酸睪酮用于治療原發(fā)性或繼發(fā)性睪丸功能減退；男孩體質(zhì)性青春期延遲；乳腺癌轉(zhuǎn)移的姑息性治療；還可以用于男性原發(fā)性或繼發(fā)性性腺功能低下的睪酮補(bǔ)充療法，例如睪丸切除后；無(wú)睪癥；垂體功能低下；內(nèi)分泌性陽(yáng)萎；由于精子生成障礙所引起的不育癥；男性更年期癥狀，例如性欲減退，腦力和體力下降等[5-7]。此外，十一酸睪酮用于男子性腺功能低下癥的睪酮替代療法，如睪丸切除以后、類無(wú)睪癥、垂體功能低下、內(nèi)分泌性陽(yáng)萎、男子更年期癥狀（性欲、腦力及體力減退等）、某些因生精功能失調(diào)而致的不育癥以及再生障礙性貧血等[8-10]。

不良反應(yīng)

十一酸睪酮作為雄激素治療可能引起的不良反應(yīng)如下：良性腫瘤、惡性腫瘤和非定性腫瘤（包括囊腫和息肉）：良性前列腺增生、前列腺癌。血液和淋巴系統(tǒng)疾患：紅細(xì)胞增多癥。代謝和營(yíng)養(yǎng)紊亂：液體和鹽潴留[11]。精神紊亂：抑郁、緊張感、情緒困擾、性欲增強(qiáng)、性欲減退。胃腸道紊亂：惡心、腹瀉、腹部不適、腹痛。肝膽病癥：淤膽型黃疸。皮膚和皮下組織疾患：瘙癢。?。ㄅc）骨骼及結(jié)締組織疾患：肌痛、骨骺早閉。血管疾患：高血壓。腎和泌尿疾患：泌尿疾病[12]。生殖系統(tǒng)和乳腺疾患：男子乳房女性化、少精、無(wú)精子、陰莖持續(xù)勃起癥、勃起頻率增加、加速性成熟、陰莖增大。肝功能異常、血清前列腺特異性抗原（PSA）升高、血紅蛋白升高、紅細(xì)胞壓積升高、血脂異常。

藥代動(dòng)力學(xué)

與睪酮不同，十一酸睪酮口服后具有活性是因?yàn)槠湟徊糠峙c乳糜微粒結(jié)合，被吸收并釋放進(jìn)入體循環(huán)淋巴液。在藥物吸收過(guò)程中，少量十一酸睪酮代謝為同樣具有活性的5α-十一酸雙氫睪酮[13]。吸收后，殘留的藥物成分在腸壁和肝臟內(nèi)代謝成無(wú)活性的生物轉(zhuǎn)化產(chǎn)物。吸收進(jìn)入淋巴液的酯類物質(zhì)經(jīng)水解，在外周循環(huán)中轉(zhuǎn)化成雌二醇。之后，這些游離類固醇向靶器官發(fā)揮雄激素活性。在穩(wěn)態(tài)條件下，單次給予本品80-160mg，4－5小時(shí)后血漿睪酮水平達(dá)到峰值，約為40nmol/l[14]。血漿睪酮水平可在服藥后維持8－12小時(shí)。消除過(guò)程與天然睪酮相同，都是通過(guò)葡萄糖醛酸反應(yīng)完成的。終產(chǎn)物主要經(jīng)腎臟排泄，少部分經(jīng)糞便排出。

毒理作用

小鼠皮下注射十一酸睪酮3.7g/kg（大鼠有效量的270倍），14天內(nèi)未發(fā)現(xiàn)死亡或異常反應(yīng)。大鼠肌內(nèi)注射十一酸睪酮每天每公斤42mg，連續(xù)6個(gè)月，未見(jiàn)明顯的肝腎功能改變或其他損害。

藥物相互作用

十一酸睪酮與環(huán)孢素合用，環(huán)孢素毒性增強(qiáng)，引發(fā)腎臟損害、膽汁淤積、感覺(jué)異常等不良反應(yīng)，應(yīng)避免合用。十一酸睪酮與腎上腺皮質(zhì)激素合用，可加重水腫。十一酸睪酮與口服抗凝藥合用，出血的危險(xiǎn)性增加[15]。十一酸睪酮與巴比妥類合用，可使本藥代謝加快，療效降低。十一酸睪酮與當(dāng)歸合用，抑制本藥代謝，增加其雄激素效應(yīng)和不良反應(yīng)發(fā)生率。糖尿病患者應(yīng)用本藥，能夠降低血糖，故應(yīng)減少胰島素的用量十一酸睪酮與紫杉醇合用，可抑制紫杉醇的代謝，導(dǎo)致毒性增強(qiáng)[16-17]。

參考文獻(xiàn)

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