Herb-drug Pharmacokinetic Interaction between Carica Papaya Extract and Amiodarone in Rats

Authors

  • Márcio Rodrigues a Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal. b CNC – Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. c CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
  • Gilberto Alves b CNC – Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. c CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
  • Joana Francisco c CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
  • Ana Fortuna a Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal. b CNC – Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
  • Amílcar Falcão a Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal. b CNC – Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

DOI:

https://doi.org/10.18433/J3559N

Abstract

Purpose - Carica papaya has been traditionally used worldwide in folk medicine to treat a wide range of ailments in humans, including the management of obesity and digestive disorders. However, scientific information about its potential to interact with conventional drugs is lacking. Thus, this work aimed to investigate the interference of a standardized C. papaya extract (GMP certificate) on the systemic exposure to amiodarone (a narrow therapeutic index drug) in rats. Methods - In the first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. papaya (1230 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in the second study, rats were pre-treated for 14 days with C. papaya (1230 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the herbal extract vehicle. Blood samples were collected before dosing and at 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h following amiodarone administration; in addition, at 24 h post-dose, blood and tissues (heart, liver, kidneys and lungs) were also harvested. Thereafter, the concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were determined in plasma and tissue samples employing a high-performance liquid chromatography-diode array detection method previously developed and validated. Results - In both studies was observed a delay in attaining the maximum plasma concentrations of amiodarone (tmax) in the rats treated with the extract. Nevertheless, it must be highlighted the marked increase (60-70%) of the extent of amiodarone systemic exposure (as assessed by AUC0-t and AUC0-∞) in the rats pre-treated with C. papaya comparatively with the control (vehicle) group. Conclusions – The results herein found suggest an herb-drug interaction between C. papaya extract and amiodarone, which clearly increase the drug bioavailability. To reliably assess the clinical impact of these findings appropriate human studies should be conducted.

This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Published

2014-07-22

How to Cite

Rodrigues, M., Alves, G., Francisco, J., Fortuna, A., & Falcão, A. (2014). Herb-drug Pharmacokinetic Interaction between Carica Papaya Extract and Amiodarone in Rats. Journal of Pharmacy & Pharmaceutical Sciences, 17(3), 302–315. https://doi.org/10.18433/J3559N

Issue

Section

Pharmaceutical Sciences; Review Articles