Gastroprotection and effect of the simultaneous administration of Cuachalalate (Amphipterygium adstringens) on the pharmacokinetics and anti-inflammatory activity of diclofenac in rats

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 C_max (7.08 ± 1.42 μg mL^-1) and AUC (12.67 ± 2.97 μg h mL^-1), but not the value of t_max (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.