Parameters of total body cholesterol metabolism in humans can be determined by using a three-pool model to analyze the turnover of plasma cholesterol following the injection of radiolabeled cholesterol. In the past this required a rigorous schedule of approximately 36 blood samples over a 10-month period. We have developed a convenient sampling schedule involving only six large samples, each analyzed in sextuplicate. Such a reduction in the frequency of samples is possible only when considerable confidence in the model is available. In general, the simplified sampling strategy depends upon considerable prior experience with the model, only moderate biological error, and estimatable subject to subject variation in model parameters. Because the timing of the samples is critical and because the optimal times will differ for different subjects, the six-point strategy involves using the first three samples (drawn at days 1, 7, and 24 or, for hypercholesterolemic subjects, at days 1, 8, and 28) in conjunction with results from previous studies to set the time for the next sample; the process is reiterated for the last two points. In this study, we have compared parameter estimates obtained by the new six-point schedule with those obtained simultaneously (in the same, single turnover study) by the old 36-point schedule in the same 26 subjects. Both schedules gave comparable values. In particular, the coefficients of variation between values obtained by the two methods for each of the four parameters for which we have developed predictive equations were quite low: PR 1.5%, M1 4.1%, M3min 13%, Mtot min 4.3%. The simplified six-point schedule makes it feasible to study long-term cholesterol turnover in substantial numbers of patients.
Blood Specimen Collection Cholesterol