We thank Dr. Phillips for his thoughtful comments. The clinical features of acute and chronic digoxin toxicity do differ. However, our purpose was not to study the clinical variables (chronicity, concomitant disease, and age) that affect how digoxin toxicity is manifested but to determine the disposition of free and total digoxin after Fab therapy and the value of free digoxin concentrations in monitoring patients. It is unlikely that whether digoxin toxicity was acute or chronic would influence the disposition of free and total digoxin after Fab therapy or the value of free digoxin concentrations. Stratification of the data according to toxicity without a strong rationale might lead to overanalysis and result in misleading interpretations. We agree that it would have been beneficial to stratify the data according to glomerular filtration rate or creatinine clearance, but this was not done.

Because we were only interested in the effects of Fab on digoxin disposition, we used the time of Fab dose as the initiation point, and it was not necessary to report the time between final digoxin dose and Fab administration.

The possible role of interfering drugs is of interest. We studied five patients who were receiving either verapamil (n = 3) or quinidine (n = 2), agents known to affect the disposition of digoxin by decreasing renal secretion. Their effect on the elimination of digoxin when Fab is present is unknown. We postulate no effect on the elimination of bound digoxin because it is attached to Fab, which is filtered but not secreted. However, these substances could decrease the secretion of free digoxin and thus alter its disposition.

We believe that digoxin-like immunoreactive substance, an agent that is extensively protein bound and thus readily removed by ultrafiltration [1], could not have affected the assays because the samples were ultrafiltrated. Previous studies have shown this substance to interfere with the assays used for measurement of total digoxin, with a magnitude of interference of 0.12 to 0.98 nmol/mL [1-3]. These values could be considered insignificant when compared with the total digoxin concentrations observed in the study patients (average peak and trough concentrations of 52 nmol/mL and 7.2 nmol/mL, respectively).