The serum pharmacokinetics of digoxin as an immunogen and hapten in the rabbit.

3H-digoxin was given intradermally 4 weeks before, and at 6 and 44 weeks after immunisation with a 3H-digoxin-human serum albumin conjugate. Before immunisation, the serum digoxin distribution and elimination half-life (t1/2) values were 4.2 h and 2.1 days respectively. The immunogen-associated radioactivity showed characteristic fluctuations during a prolonged distribution phase of about 5 days, but the t1/2 of 2.7 days was similar to that of digoxin, indicating that appreciable cleavage of digoxin from the albumin may have occurred during the distribution period. At 6 weeks after immunisation, following hapten injection there was again a prolonged distribution phase of about 5 days during which concentration of digoxin were some five-fold higher than corresponding pre-immunisation values. The serum elimination t1/2 was 4.1 days. At 44 weeks the differences were even more marked; the distribution phase was some 7 days, during which serum hapten concentrations were approximately ten-fold higher than pre-immunisation values. The serum elimination t1/2 was in this case about 25 days. Surprisingly digoxin-specific antibody titres at 6 and 44 weeks were not significantly different, indicating that measurement of titre, which is a function of both antibody concentration and affinity, is not in itself reliable in predicting changes in hapten pharmacokinetics.