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Vol. 91, No. 1-2, 2013
Issue release date: February 2013
Pharmacology 2013;91:112–116

Pharmacokinetic Interaction between Losartan and Rhodiola rosea in Rabbits

Spanakis M. · Vizirianakis I.S. · Batzias G. · Niopas I.
aDepartment of Pharmacognosy and Pharmacology, School of Pharmacy and bLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Aim: The study investigates the potential interaction of the herbal medicinal product of Rhodiola rosea on the pharmacokinetics of losartan and its active metabolite EXP3174 after concurrent oral administration to rabbits. Materials and Methods: We conducted a randomized, single-dose, two-treatment, two-period, two-sequence, cross-over pharmacokinetic study on 6 healthy female New Zealand rabbits, after concurrent oral administration of losartan (5 mg/kg) and the herbal medicinal product of R. rosea (50 mg/kg). Quantification of losartan and its main active metabolite EXP3174 was achieved using a validated HPCL/UV method. Pharmacokinetic and statistical analysis was performed using the EquivTest/PK software. Observations: Administration of the herbal medicinal product of R. rosea resulted in a statistically significant increase of the following pharmacokinetic parameters for losartan: the maximum plasma concentration (Cmax), the area under the curve (AUC) and the apparent total body clearance (CL/F). An almost 2-fold increase in the AUC of losartan was observed after concurrent administration of the herbal medicinal product of R. rosea. No statistically significant alteration was observed in the pharmacokinetic parameters of the active metabolite of losartan EXP3174. Conclusion: The data of this study suggest that R. rosea significantly alters the pharmacokinetic properties of losartan after concurrent oral administration to rabbits. A study in humans should be conducted to assess the clinical significance of a possible herb-drug interaction between the herbal medicinal products of R. rosea and drugs such as losartan, which are substrates of both CYPs and P-gp.

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