Chogtu Bharti, Ommurugan Balaji, Thomson Sereen R, Kalthur Sneha G
Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
BioPharma Solutions, Chennai, Tamil Nadu, India.
ScientificWorldJournal. 2020 Mar 31;2020:4704825. doi: 10.1155/2020/4704825. eCollection 2020.
Statin-induced myopathy is one of the major causes of poor adherence and discontinuation of this medication. There are contrary results regarding association of vitamin D insufficiency with statin-induced myopathy. This study was done to determine the effect of the vitamin D3 analogue alfacalcidol on Rosuvastatin-induced myopathy in rats. . Animals were divided into six groups with 6 rats in each group. Groups I and II acted as controls, Group III and Group IV were administered Rosuvastatin 120 mg/kg/day and 160 mg/kg/day, Groups V and VI were administered alfacalcidol 0.1 g/kg/day in addition to Rosuvastatin 120 mg/kg/day and 160 mg/kg/day, respectively. All drugs were administered orally for 15 days. Plasma creatine kinase (CK) levels were estimated on day 10 and day 15. Animals were sacrificed and muscles were sent for histopathological examination.
On day 10, Groups V and VI showed a statistically significant increase in plasma CK levels as compared to the control ( < 0.001) and were significantly lower ( < 0.001) as compared to Groups III and IV, respectively. However, on day 15, plasma CK levels in Groups V and VI were comparable to those of control groups with a nonsignificant difference ( > 0.05). On comparing the histology, Groups V and VI showed a significant difference as compared to statin-only groups (Groups III and IV) as there were signs of regeneration, less splitting, and fragmentation of muscle fibres.
The present study shows that the vitamin D analogue alfacalcidol prevents statin-induced myopathy. The serum CK levels are comparable to the control group on day 15 of vitamin D administration.
他汀类药物引起的肌病是导致该药物依从性差和停药的主要原因之一。关于维生素D缺乏与他汀类药物引起的肌病之间的关联，存在相互矛盾的结果。本研究旨在确定维生素D3类似物阿法骨化醇对大鼠瑞舒伐他汀引起的肌病的影响。动物分为六组，每组6只大鼠。第一组和第二组作为对照组，第三组和第四组分别给予瑞舒伐他汀120mg/kg/天和160mg/kg/天，第五组和第六组除分别给予瑞舒伐他汀120mg/kg/天和160mg/kg/天外，还给予阿法骨化醇0.1g/kg/天。所有药物均口服给药15天。在第10天和第15天测定血浆肌酸激酶（CK）水平。处死动物并将肌肉送去进行组织病理学检查。
在第10天，第五组和第六组的血浆CK水平与对照组相比有统计学显著升高（P<0.001），且分别与第三组和第四组相比显著降低（P<0.001）。然而，在第15天，第五组和第六组的血浆CK水平与对照组相当，差异无统计学意义（P>0.05）。在组织学比较中，第五组和第六组与仅使用他汀类药物的组（第三组和第四组）相比有显著差异，因为有再生迹象，肌肉纤维的分裂和碎片化较少。
本研究表明维生素D类似物阿法骨化醇可预防他汀类药物引起的肌病。在给予维生素D的第15天，血清CK水平与对照组相当。
