Mäenpää H, Javela K, Pikkarainen J, Mälkönen M, Heinonen O P, Manninen V
Helsinki Heart Study, Finland.
Eur Heart J. 1987 Oct;8 Suppl I:31-7. doi: 10.1093/eurheartj/8.suppl_i.31.
A direct and objective method of measuring compliance to medication is presented. Digoxin is used as a marker in capsules of either gemfibrozil or placebo with a minimal dose of 4.4 micrograms twice a day. Compliance is estimated by measuring the ratio of urinary digoxin to creatinine concentration. By choosing two cut-off points of this ratio patients who are taking their capsules regularly and those who have taken no capsules at all could be distinguished from others. Reduced dosage was easily detected in the marker results. During regular intake of three quarters of the dose, 53% of the samples would have classified the patient to the good compliance group. With half of the dose, 24% of samples and with a quarter of the dose, 5% of samples would have classified the subject to good compliance. Since the digoxin marker was planned for compliance measurements in the Helsinki Heart Study, a primary prevention study of coronary heart disease, it was tested under the conditions of a clinical trial. Digoxin concentrations were measured using a routine method normally applied to serum but shown to be valid for urine. The results of the urinary assays were not affected by storage at room temperature, as occurs during postal transport of samples, nor were they affected by freezing, routinely used for the storage of samples in clinical trials. The results therefore suggest that the digoxin marker represents a particularly effective method to study compliance to medication during such long-lasting clinical investigations.
本文介绍了一种直接且客观的测量药物依从性的方法。地高辛被用作吉非贝齐或安慰剂胶囊中的标记物，最小剂量为每日两次，每次4.4微克。通过测量尿地高辛与肌酐浓度的比值来估算依从性。通过选择该比值的两个临界点，可以将按时服药的患者和完全未服药的患者与其他患者区分开来。在标记物结果中很容易检测到剂量减少的情况。在正常服用四分之三剂量期间，53%的样本会将患者归类为依从性良好组。服用一半剂量时，24%的样本以及服用四分之一剂量时，5%的样本会将受试者归类为依从性良好。由于地高辛标记物计划用于赫尔辛基心脏研究（一项冠心病一级预防研究）中的依从性测量，因此在临床试验条件下对其进行了测试。使用通常应用于血清但已证明对尿液有效的常规方法测量地高辛浓度。尿液检测结果不受室温储存的影响（如样本在邮寄过程中那样），也不受冷冻的影响（临床试验中通常用于样本储存）。因此，结果表明地高辛标记物是在如此长期的临床研究中研究药物依从性的一种特别有效的方法。
