Menon S P, Walker R J, Duggin G G, Sullivan D R, Horvath J S, Tiller D J
Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Res Commun Chem Pathol Pharmacol. 1991 May;72(2):203-12.
The bioavailability of an oral dose of cyclosporin A (CSA) is variable. CSA is highly lipid soluble with approximately 40% of the CSA in the intravascular compartment bound to lipoproteins. This study was undertaken to determine what effect acute alterations in plasma lipids following a high fat meal would have on CSA whole blood levels 12 to 14 hours after the last dose. Fifteen renal transplant patients with stable renal function and on CSA therapy alone for a minimum of three months were investigated. Anthropometric data was recorded and baseline blood samples were drawn for CSA, liver function, renal function, vitamins A and E. triglycerides, cholesterol and lipoproteins following an overnight fast. The subjects then received a high fat (72.8% of caloric value) or a low fat (12% of caloric value) meal and post-prandial samples were drawn at two and four hours. The correlation between CSA levels (r = 0.72) taken on the two study days (one week apart) was less than expected despite no change in dosage. Cholesterol levels remained unchanged but triglyceride levels rose following the high fat meal. CSA levels did not correlate with the post-prandial changes in triglycerides, nor with any other parameter of lipid metabolism, lipid transport, or total body fat. This study demonstrated that CSA whole blood levels are not influenced by acute variations in lipids following a meal and therefore the time of sampling for a CSA trough level will not be influenced by the proximity to a recent meal.
口服剂量的环孢素A(CSA)的生物利用度存在差异。CSA具有高度脂溶性,血管内的CSA约40%与脂蛋白结合。本研究旨在确定高脂餐后血浆脂质的急性变化对末次给药后12至14小时CSA全血水平有何影响。对15例肾功能稳定且仅接受CSA治疗至少三个月的肾移植患者进行了研究。记录人体测量数据,并在空腹过夜后采集基线血样,检测CSA、肝功能、肾功能、维生素A和E、甘油三酯、胆固醇和脂蛋白水平。然后,受试者分别接受高脂餐(热量值的72.8%)或低脂餐(热量值的12%),并在餐后两小时和四小时采集血样。尽管剂量未变,但在两个研究日(相隔一周)采集的CSA水平之间的相关性(r = 0.72)低于预期。高脂餐后胆固醇水平保持不变,但甘油三酯水平升高。CSA水平与餐后甘油三酯的变化无关,也与脂质代谢、脂质转运或体脂的任何其他参数无关。本研究表明,餐后脂质的急性变化不会影响CSA全血水平,因此,CSA谷浓度的采样时间不会受到与最近一餐时间接近程度的影响。