The Combination of Amoxicillin and 1,8-Cineole Improves the Bioavailability and the Therapeutic Effect of Amoxicillin in a Rabbit Model

In this study, the effectiveness of the combination therapy of 1,8-cineole with amoxicillin (AMX) and clavulanic acid (Clav) was investigated. For this, the pharmacokinetic behaviors of AMX in rabbits were studied after a single oral dose. The animals were divided randomly into two groups: the reference group (received AMX/Clav (50/12.5 mg/kg)) and the test group (received AMX/Clav/1,8-cineole (50/12.5/10 mg/kg)). Blood samples were collected prior to administration and after T1h, T2h, T3h, and T6h post-administration. Plasma concentrations of AMX were quantified using a validated HPLC method. The antibacterial activity of plasma and cerebrospinal fluid (CSF) of treated rabbits was tested against Escherichia coli ESBL-producing a strain by microdilution method. The obtained results showed significant differences in pharmacokinetic parameters between the two groups. The resulting AUC(0-6h) and C-max mean values of the AMX reference group were 14.74 mu g.h/mL and 3.49 mu g/mL, respectively. However, those of the AMX test group were 22.30 mu g.h/mL and 5.79 mu g/mL, respectively. The results showed that the antibacterial activity of the plasma and CSF test group was significantly higher than that of the reference group. The effectiveness of this combination (Olipen: AMX/Clav/1,8-cineole) was demonstrated by increasing the level of the antibiotic and by improving the bioavailability.