title: Investigating herb-drug interactions: the effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats.
abstract: Citrus aurantium extract has been largely used in weight loss and sports performance dietary supplements. However, the safety of C. aurantium-containing products has been questioned mainly due to the association of its use with adverse events in the cardiovascular system. Therefore, this work aimed to assess the potential for herb-drug interactions among a standardized C. aurantium extract (GMP certificate) and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. aurantium (164 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in a second study, rats were pre-treated during 14 days with C. aurantium (164 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Overall, after analysis of the pharmacokinetic data, it deserves to be highlighted the significant increase of the peak plasma concentration of amiodarone in rats pre-treated with C. aurantium extract, while the extent of systemic exposure was comparable between both groups. This paper reports, for the first time, data on the potential of herb-drug interaction between C. aurantium extract and amiodarone. However, specific clinical trials should be performed to confirm these results in humans.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Márcio
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Gilberto
authors.initials: G
authors.lastname: Alves
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
mesh_terms: D000284:Administration, Oral; D000638:Amiodarone / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001835:Body Weight; D002957:Citrus / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005638:Fruit / Q000737:chemistry*; D006207:Half-Life; D041743:Herb-Drug Interactions; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010936:Plant Extracts; D000638:Amiodarone
keywords: AM; AUC; AUC from time zero to infinite; AUC from time zero to the last sampling time; AUC(0−)(t); AUC(0−∞); Amiodarone; C(last); C(max); CYP; Citrus aurantium; FDA; Food and Drug Administration; Herb–drug interaction; LOQ; MDEA; MRT; P-glycoprotein; P-gp; Pharmacokinetics; Rats; SD; UV; amiodarone; apparent terminal elimination half-life; apparent terminal rate constant; area under the concentration-time curve; cytochrome P450; i.p.; intraperitoneal; k(el); last quantifiable concentration; limit of quantification; mean residence time; mono-N-desethylamiodarone; peak concentration; standard deviation; t(1/2el); t(max); time to reach C(max); ultraviolet detection