Samuel P, Holtzman C H, Meilman E, Perl W
J Clin Invest. 1968 Aug;47(8):1806-18. doi: 10.1172/JCI105870.
Five patients received cholesterol-7alpha-(3)H intravenously during control periods. Specific activity of total serum cholesterol was determined serially during the 1st wk and weekly thereafter. 28-59 wk after the injection of the tracer, when no further radioactivity could be detected in serum cholesterol, 2 g of oral neomycin was given daily to four patients for the remainder of the experiment. Average total serum cholesterol concentrations were reduced by 20, 21, 26, and 29%, respectively, in these subjects. The fifth patient, given placebo, had no change in serum cholesterol. After a period of 12-26 wk of medication the intravenous injection of cholesterol-7alpha-(3)H was repeated, and while neomycin or placebo administration was continued, serum cholesterol specific activity was again determined serially during the 1st wk and weekly thereafter for 23-42 wk. The data were subjected to a two-compartment analysis. During the administration of neomycin, half-times of the cholesterol radio-activity decay curves were decreased in two patients and remained unchanged in two subjects. The size of the "intermediate" pool of cholesterol decreased in each patient during the administration of neomycin by 33, 36, 40, and 44%, respectively. The absolute decrease was much larger in each case than the concomitant reduction of serum cholesterol. There was no significant change in the data during the administration of placebo in one patient. The size of the "intermediate" pool can be calculated by compartmental analysis from the cholesterol decay curves. For the "slow" pool size and the other kinetic parameters only ranges of values can be deduced from the present experiment.
5名患者在对照期静脉注射胆固醇-7α-(3)H。在第1周期间连续测定总血清胆固醇的比活性,此后每周测定一次。在注射示踪剂后28 - 59周,当血清胆固醇中检测不到进一步的放射性时,在实验的剩余时间里,每天给4名患者口服2g新霉素。这些受试者的平均总血清胆固醇浓度分别降低了20%、21%、26%和29%。第5名接受安慰剂的患者血清胆固醇没有变化。在用药12 - 26周后,再次静脉注射胆固醇-7α-(3)H,在继续给予新霉素或安慰剂的同时,在第1周期间再次连续测定血清胆固醇比活性,此后每周测定一次,持续23 - 42周。对数据进行双室分析。在给予新霉素期间,两名患者胆固醇放射性衰变曲线的半衰期缩短,两名受试者保持不变。在给予新霉素期间,每名患者胆固醇“中间”池的大小分别减少了33%、36%、40%和44%。在每种情况下,绝对减少量都远大于同时期血清胆固醇的降低量。一名患者在给予安慰剂期间数据无显著变化。“中间”池的大小可以通过对胆固醇衰变曲线进行房室分析来计算。对于“慢”池大小和其他动力学参数,只能从本实验中推导出数值范围。