Pharmacokinetic Interaction between Losartan and Rhodiola rosea in Rabbits

Department of Pharmacognosy and Pharmacology, School of Pharmacy, Thessaloniki, Greece.
Pharmacology (Impact Factor: 1.67). 01/2013; 91(1-2):112-116. DOI: 10.1159/000345929
Source: PubMed


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.

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 (C(max)), 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.

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.

172 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 was investigated in the mouse formalin test. Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B1+B6+B12 by using the ED30 and a fixed 1:1 ratio combination. Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED50=81mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K(+) channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED30 values were significantly smaller than those calculated theoretically. These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 08/2013; 20(14). DOI:10.1016/j.phymed.2013.07.006 · 3.13 Impact Factor
  • Source
    5th International BBBB conference / Abstract book European Journal of Pharmaceutical Sciences, Athens; 09/2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/aim: It is significant for patients with traumatic brain injury (TBI) to receive prehospital emergency treatment as early as possible to reduce mortality. Therefore, a new prefilled multi-drug injector was developed to improve the treatment of TBI. Here, we studied the pharmacokinetics of dexamethasone (DXM) and nefopam using the injector to investigate the significance of drug interactions and the necessity of dose adjustment. Methods: Rats were administered DXM and nefopam intramuscularly alone or in combination using the injector. The concentrations of DXM and nefopam were measured by means of HPLC. The noncompartmental approach was used to calculate pharmacokinetic parameters. Results: All animals appeared to tolerate the injection very well. The maximum concentration 90% confidence interval (CI) of nefopam was in the bioequivalence range when nefopam was co-administered with DXM. However, the AUC 90% CI of nefopam was out of the range. A statistically significant alteration was also observed in the clearance of nefopam. The co-administration exhibited no significant influence on the pharmacokinetic parameters of DXM. Conclusions: These results indicate that the co-administration of DXM and nefopam using the prefilled multi-drug injector significantly alters some pharmacokinetic parameters of nefopam and has a minor effect on DXM pharmacokinetics.
    Pharmacology 07/2014; 93(5-6):220-224. DOI:10.1159/000362844 · 1.67 Impact Factor