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. 2022 Sep 22;11(10):1294.
doi: 10.3390/antibiotics11101294.

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

Ahmed Amin Akhmouch  1 , Soukayna Hriouech  1 , Hanane Chefchaou  2 , Mariam Tanghort  2 , Aouatef Mzabi  2 , Najat Chami  1 , Adnane Remmal  1
Affiliations

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

Ahmed Amin Akhmouch et al. Antibiotics (Basel). .

Abstract

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 AUC0-6h and Cmax mean values of the AMX reference group were 14.74 µg.h/mL and 3.49 µg/mL, respectively. However, those of the AMX test group were 22.30 µg.h/mL and 5.79 µg/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.

Keywords: 1,8-cineole; Escherichia coli ESBL; amoxicillin; bioavailability; clavulanic acid; combination therapy; pharmacokinetic parameters; rabbit model.

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Conflict of interest statement

The authors declare that there is no conflict of interest related to this research paper.

Figures

Figure 1
Figure 1
Chromatographic analysis of AMX: (A) plasma blank; (B) plasma + internal standard (cefadroxil 20 µg/mL); (C) plasma + AMX (10 µg/mL) + internal standard (cefadroxil 20 µg/mL).
Figure 2
Figure 2
Curves of the mean plasma concentration of AMX for reference and test groups vs. time (h) at a semilogarithmic scale. *: statistically significant difference compared to reference group (p < 0.05). **: statistically significant difference compared to reference group (p < 0.01).
Figure 3
Figure 3
Effects of plasma samples collected from animals treated with AMX/Clav (reference group) or with AMX/Clav/1,8-cineole (test group) against E. coli ESBL-producing strain growth (inhibition%). *: statistically significant difference compared to reference group (p < 0.05); ***: statistically significant difference compared to reference group (p < 0.001).
Figure 4
Figure 4
Effects of cerebrospinal fluid (CSF) samples collected from animals treated with AMX/Clav (reference group) or with AMX/Clav/1,8-cineole (test group) against E. coli ESBL-producing strain growth (inhibition%). **: statistically significant difference compared to reference group (p < 0.01); ***: statistically significant difference compared to reference group (p < 0.001).
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