title: Herb-drug pharmacokinetic interaction between carica papaya extract and amiodarone in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: 1 Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal. 2 CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. 3 CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, Covilhã, Portugal.
authors.forename: Márcio
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Gilberto
authors.initials: G
authors.lastname: Alves
authors.forename: Joana
authors.initials: J
authors.lastname: Francisco
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuna
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
mesh_terms: D000284:Administration, Oral; D000638:Amiodarone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D029441:Carica / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry; D041743:Herb-Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010936:Plant Extracts; D000638:Amiodarone