title: Gastroprotection and effect of the simultaneous administration of Cuachalalate (Amphipterygium adstringens) on the pharmacokinetics and anti-inflammatory activity of diclofenac in rats.
abstract: This work aimed to study the effect of Cuachalalate methanol extract (CME) on the anti-inflammatory activity and pharmacokinetics of diclofenac sodium, a frequently prescribed non-steroidal anti-inflammatory drug (NSAID). The gastroprotective effect of CME on the gastric injury induced by diclofenac was studied in rats. CME showed a gastroprotective effect of 15.7% at 1 mg kg(-1) and 72.5% at dose of 300 mg kg(-1). Omeprazole, used as anti-ulcer reference drug, showed gastroprotective effects of 50-89.7% at doses tested (1-30 mg kg(-1)). The value of the 50% effective dose for the anti-inflammatory effect of diclofenac sodium (ED50 = 1.14 +/- 0.23 mg kg(-1)) using carrageenan-induced rat paw oedema model, was not modified by the concomitant administration of 30 or 100 mg kg(-1) of CME. The effect of CME (30, 100 and 300 mg kg(-1), p.o.) on the pharmacokinetics of diclofenac sodium was studied. It was observed that the simultaneous administration of diclofenac sodium and 300 mg kg(-1) of CME decreased significantly the values of Cmax (7.08 +/- 1.42 microg mL(-1)) and AUC (12.67 +/- 2.97 microg h mL(-1)), but not the value of tmax (0.13 (0.1-0.25)h) obtained with the administration of diclofenac alone. The simultaneous administration of 30 or 100 mg kg(-1) of CME did not modify the pharmacokinetic parameters of diclofenac. The experimental findings in rats suggest that CME at doses lower than 100 mg kg(-1) protects the gastric mucosa from the damage induced by diclofenac sodium without altering either the anti-inflammatory activity or the pharmacokinetics of this NSAID.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria Coyoacan 04510, México DF, México. anavarrt@servidor.unam.mx
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarrete
authors.forename: Iván
authors.initials: I
authors.lastname: Oliva
authors.forename: María Elena
authors.initials: ME
authors.lastname: Sánchez-Mendoza
authors.forename: Jesús
authors.initials: J
authors.lastname: Arrieta
authors.forename: Leticia
authors.initials: L
authors.lastname: Cruz-Antonio
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
mesh_terms: D027926:Anacardiaceae / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010936:Plant Extracts; D004008:Diclofenac