I The properties of a recently introduced digitalis glycoside, 4-,-methyl digoxin (medigoxin)were compared to those of a standard digoxin preparation. Using a radioimmunoassay (RIA) technique, serial plasma levels were recorded for 8 h following a single oral dose in five fasting volunteer subjects, and urinary glycoside elimination was measured for 4 consecutive days after dosage by use of a modification of the RIA method. 2 It was found that this RIA was suitable for plasma level measurement of both digoxin and midigoxin by reference to appropriate standard curves. Comparison of the plasma level profiles of these two drugs showed that medigoxin was very rapidly absorbed with peak levels occurring within 15-30 min, while digoxin produced peak levels after 45-75 min. The area under the plasma level-time curve produced by medigoxin was also consistently greater than that produced by digoxin, even though the medigoxin dose used was smaller. Quantitative comparison of these areas after adjustment to compensate for differing doses showed that medigoxin is considerably more biologically available than digoxin under study conditions (ratio 1.6 + 0.25: 1), and comparison of quantitative urinary elimination suggested that medigoxin is eliminated in the urine to a lesser extent than digoxin and therefore it undergoes more metabolism and/or hepato-biliary elimination.
SYNOPSISAn extremely rapid radioimmunoassay for digoxin is described which is precise over the range of concentrations required to determine whether, or not, a patient has digoxin toxicity. The assay is based on the use of 125-iodine-labelled digoxin and of a gel equilibration technique for the separation of antibody-bound and free digoxin. The results obtained compare closely with those by a conventional radioimmunoassay and the technique is sufficiently simple to enable its performance by relatively inexperienced laboratory staff.Since Butler and Chen (1967) described a method for producing antibodies to the cardiac glycosides, many radioimmunoassays for digoxin have been developed. It is now becoming apparent that a variety of such assays are needed according to the nature and urgency of a request.1 A rapid but relatively insensitive assay is required for urgent samples from patients with suspected digoxin toxicity. Such requests are relatively infrequent; however, results are required with a minimum of delay and the assay should cover the clinically important range of concentrations (1 to 4 ng/ml). Furthermore, the assay should, ideally, be so simple technically that it can be performed by laboratory personnel who are inexperienced in radioimmunoassay, since it is unlikely that experienced radioimmunoassayists will always be available.2 A routine assay is required suitable for large numbers of samples from patients maintained on digoxin to ensure adequate control of their therapy. In this situation a rapid result is unnecessary but attention should be given to precision and cost.3 A highly sensitive assay is required suitable for research samples and for the very small blood samples obtained by heelprick in neonatal practice.This paper describes an assay developed to fulfil the requirements of the first type. It is based on the use of 1251-digoxin as tracer and of a gel equilibration technique for the separation of antibodybound and free digoxin.
Materials and MethodsDixogin standards, ranging from 05 to 8-0 ng/ml, were made up in digoxin-free plasma from stock
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