Akhmouch Ahmed Amin, Hriouech Soukayna, Chefchaou Hanane, Tanghort Mariam, Mzabi Aouatef, Chami Najat, Remmal Adnane
Department of Biology, Faculty of Science Dhar El Mahraz, University Sidi Mohammed Ben Abdellah, Fez 30050, Morocco.
Systems and Sustainable Environment Laboratory, Private University of Fez UPF, Fez 30000, Morocco.
Antibiotics (Basel). 2022 Sep 22;11(10):1294. doi: 10.3390/antibiotics11101294.
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 ESBL-producing a strain by microdilution method. The obtained results showed significant differences in pharmacokinetic parameters between the two groups. The resulting AUC and C 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.
在本研究中，考察了1,8-桉叶素与阿莫西林（AMX）和克拉维酸（Clav）联合治疗的有效性。为此，研究了家兔单次口服给药后AMX的药代动力学行为。将动物随机分为两组：参照组（接受AMX/Clav（50/12.5mg/kg））和试验组（接受AMX/Clav/1,8-桉叶素（50/12.5/10mg/kg））。在给药前以及给药后1小时、2小时、3小时和6小时采集血样。采用经过验证的高效液相色谱法对AMX的血浆浓度进行定量。通过微量稀释法检测治疗家兔的血浆和脑脊液（CSF）对产ESBL菌株的抗菌活性。所得结果表明两组之间的药代动力学参数存在显著差异。AMX参照组的AUC和C均值分别为14.74µg·h/mL和3.49µg/mL。然而，AMX试验组的分别为22.30µg·h/mL和5.79µg/mL。结果表明，试验组血浆和脑脊液的抗菌活性显著高于参照组。通过提高抗生素水平和改善生物利用度，证明了这种联合用药（Olipen：AMX/Clav/1,8-桉叶素）的有效性。
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