Al-Asmari Abdulrahman K, Ullah Zabih, Al-Sabaan Fahad, Tariq Mohammad, Al-Eid Ahmed, Al-Omani Saud F
Research Center, Prince Sultan Medical Military City, P.O. Box k-486, Riyadh, 11159, Saudi Arabia,
Eur J Drug Metab Pharmacokinet. 2015 Mar;40(1):87-94. doi: 10.1007/s13318-014-0183-z. Epub 2014 Apr 18.
The 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors known as "statins" are widely prescribed for the management of dyslipidemia. In spite of their muscle toxicity, use of statins has alarmingly increased worldwide. A recent report suggests that vitamin D (VD) levels are closely associated with lipid lowering activity and muscular toxicity of statins. However, data are limited and inconclusive. The present study was undertaken to investigate the effect of VD supplementation on the bioavailability and lipid lowering effect of simvastatin (ST). Adult Sprague-Dawley male rats (250 ± 10 g) were divided into four groups including control, ST (100 mg/kg/day), VD (100 μg/kg/day) and ST + VD group, respectively. After the dosing period of 8 days the animals were sacrificed and the blood was collected for the analysis of ST, its active metabolite simvastatin acid (STA), total cholesterol, triglyceride and liver enzymes including aspartate transaminase and alanine transaminase. The result of this study showed a significant decrease in the level of cholesterol and triglyceride in ST alone treated group, whereas VD alone failed to alter the blood lipid levels. Concomitant treatment with VD produced significant decrease in the bioavailability of ST and STA. However, there was no significant difference in the level of cholesterol in ST alone and in ST + VD treated group. Our results on the liver enzyme suggest that ST alone or in combination with VD does not produce any hepatotoxicity. Further studies using VD along with various statins for a longer duration are suggested.
被称为“他汀类药物”的3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）抑制剂被广泛用于治疗血脂异常。尽管存在肌肉毒性，但他汀类药物在全球的使用量仍惊人地增加。最近的一份报告表明，维生素D（VD）水平与他汀类药物的降脂活性和肌肉毒性密切相关。然而，数据有限且尚无定论。本研究旨在探讨补充VD对辛伐他汀（ST）生物利用度和降脂效果的影响。将成年Sprague-Dawley雄性大鼠（250±10 g）分为四组，分别为对照组、ST组（100 mg/kg/天）、VD组（100 μg/kg/天）和ST + VD组。给药8天后处死动物，采集血液分析ST、其活性代谢产物辛伐他汀酸（STA）、总胆固醇、甘油三酯以及包括天冬氨酸转氨酶和丙氨酸转氨酶在内的肝酶。本研究结果显示，单独使用ST治疗的组中胆固醇和甘油三酯水平显著降低，而单独使用VD未能改变血脂水平。VD联合治疗使ST和STA的生物利用度显著降低。然而，单独使用ST组和ST + VD治疗组的胆固醇水平没有显著差异。我们关于肝酶的结果表明，单独使用ST或与VD联合使用均不会产生任何肝毒性。建议进一步开展更长时间的VD与各种他汀类药物联合使用的研究。
