Variances in pharmacokinetic parameters due to assay methods for beta-methyldigoxin.

ABSTRACT

A digoxin radioimmunoassay (RIA) or fluorescence polarization immunoassay (FPIA) kit is frequently used in routine therapeutic drug monitoring (TDM) of beta-methyldigoxin (MD) by applying a calibration curve made using the corresponding digoxin calibrators. The variances in the plasma levels (61 samples) and pharmacokinetics (5 patients) due to these two different assay methods for MD were examined in our patients with congestive heart failure. Although the plasma levels of MD measured by these methods were well correlated (r = 0.956, p less than 0.001) to each other over a wide range, RIA showed significantly lower values (p less than 0.01) in the subtherapeutic range (less than 0.80 ng/ml), but significantly higher values (p less than 0.002) in the therapeutic and toxic ranges (0.80-2.00 and 2.00 less than ng/ml), respectively than FPIA. This trend occurred with increasing concentrations. When MD samples, spiked in normal human plasma, were analyzed by these methods, RIA showed almost true MD values and gave larger values than FPIA with a mean ratio of FPIA to RIA of 0.83. In contrast, normal plasma samples, each spiked with a MD metabolite such as digoxigenin-bisdigitoxide or digoxigenin-monodigitoxide, showed higher values by 10 to 22% in FPIA. These observations are in good agreement with the findings obtained in a pharmacokinetic study that RIA gave significantly higher levels than FPIA, only in the early stage after MD administration, resulting in a smaller total volume of distribution and a larger beta value in the elimination phase, as compared with FPIA.(ABSTRACT TRUNCATED AT 250 WORDS)