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

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.

Study on the Role of the Inclusion Complexes with 2-Hydroxypropyl-β-cyclodextrin for Oral Administration of Amiodarone

“…It was noted that the C max obtained following the oral administration of a single dose of formulation Fc in rats was 1.5 and 3.8 times higher in comparison to the C max obtained following formulation F and pure AMD suspension oral administration, respectively. The values of the AMD plasma concentrations released from Fc formulation independent of time belong to <2000 ng mL -1 , the same therapeutic interval as that found by other authors for humans [68,69], and these values are similar with those reported in other studies concerning the pharmacokinetic studies using rats [70][71][72]. After 24 h from administration, the values of the plasma concentration released from Fc are also higher than those of the two control samples.…”

Anti-inflammatory and immunomodulatory properties of Carica papaya

“…The possibilities of side effects (such as allergic reactions, changes in hematology parameters and gastric irritation) associated with consumption or topical application of high doses of papaya preparations are indicated (Oduola et al 2007;Duru et al 2012;Enaibe et al 2014; http://www.drugs.com/npp/papaya.html). There are only a few scientific studies that have reported interactions between papaya components and synthetic conventional drugs (Fakeye et al 2007;Rodrigues et al 2014). For further confirmation of anti-inflammatory and immunomodulatory effects, as well as of any side effects and drug interactions with papaya extracts, double-blind placebo-controlled clinical trials still need to be carried out.…”

Carbamazepine Shows Plasma and Tissue Pharmacokinetic Interactions with Ajuga bracteosa Extract in Rats

“…A significant difference (p < 0.01) in CBZ concentrations was revealed at all the time points in the pre-treated group as compared to the control group-I. The pre-treatment study was conducted to observe the time-dependent inhibition/induction effect of ABCE on the pharmacokinetics of CBZ in line with a previous study design [41]. Pre-treatment also mimics a situation where the ABCE utilized for some time, is followed by the use of the CBZ or other dual substrate drugs.…”