Effects of multiple doses of montmorillonite, alone and in combination with activated charcoal, on the toxicokinetics of a single dose of digoxin in rats

Document Type : Original Article


1 Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Clinical Toxicology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Pharmaceutical and Food Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

7 Student Research Committee, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

8 International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

9 Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s): A narrow margin between the therapeutic and toxic doses of digoxin can result in an increased incidence of toxicity.  Since digoxin has an enterohepatic cycle, multiple oral doses of absorbents like montmorillonite may be useful in the treatment of digoxin toxicity.
Materials and Methods: In this study, 4 groups of 6 rats received intraperitoneal digoxin (1 mg/kg), and half an hour later, distilled water (DW) or oral adsorbents, including montmorillonite (1 g/kg), activated charcoal (1 g/kg) (AC) alone or in combination in the ratio of 70:30. Half of the mentioned doses were also gavaged at 3 and 5.5 hr after digoxin injection. The serum level of digoxin, biochemical factors, and activity score were assessed during the experiment. Three control groups only received DW, montmorillonite, or AC.
Results: All adsorbents were able to significantly decrease the serum level of digoxin compared to the digoxin+DW group (P<0.01). Only montmorillonite reversed the digoxin-induced hyperkalemia (P<0.05). Multiple dose administration of adsorbents also significantly reduced the digoxin area under the curve and half-life and increased digoxin clearance (P<0.05). However, there was no significant difference in the kinetic parameters between groups that received digoxin plus adsorbents.
Conclusion: Multiple-dose of montmorillonite reversed digoxin toxicity and reduced serum digoxin levels by increasing the excretion and reducing the half-life. Montmorillonite has also corrected digoxin-induced hyperkalemia.  Based on the findings, a multiple-dose regimen of oral montmorillonite could be a suitable candidate for reducing the toxicity issue associated with drugs like digoxin that undergo some degree of enterohepatic circulation.


Main Subjects

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