Minimal doses of digoxin: a new marker for compliance to medication.

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.