Effect of purple grape juice on the pharmacokinetics of digoxin:
Results of a food-drug interaction study
Xia Song1, Yang Ju2, Hui Zhao3, Wen Qiu1
1 Department of Clinical Pharmacy, 2 Department of Drug Research and Development, and 3 Department of Drug Regulatory, Lanzhou University Second Hospital, Lanzhou, Gansu, China
DOI 10.5414/CP203273
Abstract
Objective: Digoxin is a glycosidic, cardiotonic plant extract with a narrow therapeutic window. The purpose of the study was to investigate the effects of purple grape juice on the pharmacokinetics of digoxin in rats. Materials and methods: A randomized, controlled, single- and multiple-dose study was conducted to evaluate the pharmacokinetic profiles of orally and intravenously administered digoxin. The plasma concentration of digoxin was determined by radioimmunoassay using a gamma counter, and a Caco-2 cell transport model was used to investigate the potential mechanism by which purple grape juice affects the pharmacokinetics of digoxin. Results: The results show that multiple-dose purple grape juice caused a remarkable increase in the AUC, C<sub>max</sub>, and Ka of orally administered digoxin (p < 0.05); only a single dose increased the digoxin AUC<sub>0–∞</sub> by 72.80% (p < 0.05). Other parameters were not significantly affected. The study of intravenously administered digoxin found no significant difference in the pharmacokinetic characteristics of the two dosing groups (p > 0.05). The Caco-2 transwell experiments indicated that both the pure purple grape juice and its ethyl acetate extract significantly inhibited digoxin basolateral-to-apical (B→A) transport at concentrations of 10%, 30%, and 50% with dose dependency. These results confirmed that the improvement in bioavailability of digoxin resulted from the inhibition of P-gp by purple grape juice at the level of the gastrointestinal wall. Conclusion: Purple grape juice can increase the bioavailability of orally administered digoxin, especially with multiple doses. This information suggests that co-administration of oral digoxin and purple grape juice may require a dose adjustment.
Author Details
Authors
Departments
- 1 Department of Clinical Pharmacy,
- 2 Department of Drug Research and Development, and
- 3 Department of Drug Regulatory, Lanzhou University Second Hospital, Lanzhou, Gansu, China
Address
Wen Qiu, PD
Lanzhou University Second Hospital
Cuiying men Road 82#, Lanzhou 730030, China
Email:
[email protected]
Citation
Xia Song, Yang Ju, Hui Zhao, and Wen Qiu.Effect of purple grape juice on the pharmacokinetics of digoxin:
Results of a food-drug interaction study
. 2019; 57: 101-109. doi: 10.5414/CP203273.
