Pharmacokinetic study of beta-methyldigoxin by enzyme immunoassay using a novel specific antiserum in rats.
We previously showed that enzyme immunoassay (EIA) of beta-methyldigoxin (MDx3) using anti-MDx3 3'-hemisuccinate-bovine serum albumin antiserum (Antiserum-I) was superior to that using commercial anti-digoxin antiserum (Antiserum-II) in terms of specificity and that pretreatment of human serum with phenyl boric acid (PBA) column was effective. In the present study, we examined the precision of EIA using Antiserum-I and the recovery of MDx3 after PBA column treatment in rat serum, and also investigated pharmacokinetic changes of MDx3 in rats. The intra- and inter-assay variations and recovery tests using Antiserum-I were good. The PBA column was effective in selectively separating MDx3 from rat serum containing MDx3 and its metabolites. The recovery tests using Antiserum-I with PBA column showed about 110% and the interference of metabolites of MDx3 was negligible. Serum concentration-time courses of MDx3 by EIA using Antiserum-I with PBA column and Antiserum-I were lower than that using Antiserum-II. The distribution volume at steady state and total body clearance values of MDx3 in these conditions were significantly higher than those using Antiserum-II. The usefulness of PBA column was ascertained, while effects of PBA column on these parameters were not significant. In addition, rapid absorption of MDx3 was observed by EIA using Antiserum-I with PBA column. These results suggest that EIA using Antiserum-I with PBA column for the pretreatment of serum samples should be a more useful and valuable system in therapeutic drug monitoring and pharmacokinetic studies of the unchanged type of MDx3 than Antiserum-II.
Higashi
Yasuhiko
Y
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. y-higashi@hokuriku-u.ac.jp
Watanabe
Naomi
N
Sasaki
Toshiyuki
T
Fujii
Youichi
Y
D000818:Animals; D007106:Immune Sera / Q000032:analysis*; D007124:Immunoenzyme Techniques / Q000379:methods*; D008297:Male; D008520:Medigoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D007106:Immune Sera; D008520:Medigoxin