Department of Intensive Care, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Department of Clinical Pharmacy, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
J Oncol Pharm Pract. 2021 Jan;27(1):216-219. doi: 10.1177/1078155220923001. Epub 2020 May 12.
Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown.
We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin.
Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone.
Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.
醋酸阿比特龙是一种雄激素生物合成抑制剂，已被批准用于治疗去势抵抗性前列腺癌和转移性去势敏感性前列腺癌。阿比特龙很少与严重横纹肌溶解症相关，但肌肉毒性的机制尚不清楚。
我们在此介绍一例严重横纹肌溶解症病例，患者在开始使用醋酸阿比特龙前正在服用瑞舒伐他汀，随后发生了慢性肾损伤的急性加重。
横纹肌溶解症在停用瑞舒伐他汀和醋酸阿比特龙后得到缓解，肾功能恢复。单独重新开始使用醋酸阿比特龙后，肌肉毒性未再复发。
醋酸阿比特龙选择性抑制 CYP17 以及肝转运蛋白 OATP1B1。OATP1B1 是一种外排转运蛋白，其功能是从门静脉血液中提取几种药物，使它们能够进行肝代谢。我们假设，阿比特龙抑制 OATP1B1 对瑞舒伐他汀的血浆摄取，增加了瑞舒伐他汀的血浆浓度，导致肌肉细胞毒性。因此，我们建议避免瑞舒伐他汀与阿比特龙联合使用。
