Lindenthal B, Simatupang A, Dotti M T, Federico A, Lütjohann D, von Bergmann K
Department of Clinical Pharmacology, University of Bonn, Germany.
J Lipid Res. 1996 Oct;37(10):2193-201.
Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis. In normolipemic volunteers, excretion of mevalonic acid averaged 3.51 +/- 0.59 (SD) micrograms/kg x day1; (n = 24) and was not different from patients with hypercholesterolemia (3.30 +/- 0.92 micrograms/kg x day1; n = 24). In patients with cerebrotendineous xanthomatosis, the excretion was significantly higher (8.55 +/- 1.92 micrograms/kg x day1; n = 6, P < 0.001) but comparable to volunteers treated with cholestyramine (6.69 +/- 2.6 micrograms/kg x day1; n = 5). A significant correlation was found between 24-h excretion of mevalonic acid and cholesterol synthesis (r = 0.835; n = 35; P < 0.001). The coefficient of variation of excretion of mevalonic acid during 3 consecutive days was small (9.8%; n = 7). However, urinary output of mevalonic acid was significantly higher during the night (164 +/- 14 micrograms/12-h) than during the day (129 +/- 9 micrograms/12-h; n = 11; P < 0.05). In patients treated with simvastatin (40 mg/day) for 6 weeks, the ratio of mevalonic acid to creatinine in a morning urine sample decreased significantly compared to pretreatment values (110 +/- 25 micrograms/g vs. 66 +/- 25 micrograms/g; P < 0.001). Furthermore, the ratio of mevalonic acid to creatinine in a morning urine sample correlated with the ratio from the 24-h collection period (r = 0.714; n = 34; P < 0.001). The results indicate that the analysis of urinary mevalonic acid, either in 24-h collection or in a single morning sample, is an attractive method for evaluation of long and very short term changes of the rates of cholesterol synthesis.
研究了甲羟戊酸的尿排泄情况，以此作为胆固醇合成的指标。在血脂正常的志愿者中，甲羟戊酸的排泄量平均为3.51±0.59（标准差）微克/千克·天¹；（n = 24），与高胆固醇血症患者（3.30±0.92微克/千克·天¹；n = 24）无差异。在脑腱性黄瘤病患者中，排泄量显著更高（8.55±1.92微克/千克·天¹；n = 6，P < 0.001），但与用消胆胺治疗的志愿者（6.69±2.6微克/千克·天¹；n = 5）相当。发现甲羟戊酸的24小时排泄量与胆固醇合成之间存在显著相关性（r = 0.835；n = 35；P < 0.001）。连续3天甲羟戊酸排泄量的变异系数较小（9.8%；n = 7）。然而，甲羟戊酸的夜间尿量（164±14微克/12小时）显著高于白天（129±9微克/12小时；n = 11；P < 0.05）。在用辛伐他汀（40毫克/天）治疗6周的患者中，晨尿样本中甲羟戊酸与肌酐的比值与治疗前值相比显著降低（110±25微克/克对66±至25微克/克；P < 0.001）。此外，晨尿样本中甲羟戊酸与肌酐的比值与24小时收集期的比值相关（r = 0.714；n = 34；P < 0.001）。结果表明，无论是24小时收集还是单次晨尿样本中尿甲羟戊酸的分析，都是评估胆固醇合成速率长期和非常短期变化的一种有吸引力的方法。
