Pharmacokinetic profile of amoxicillin and its glucuronide‐like metabolite when administered subcutaneously to koalas (Phascolarctos cinereus). Issue 2 (10th June 2019)

• Record Type: Journal Article
• Authors: Kimble, Benjamin; Vogelnest, Larry; Gharibi, Soraya; Izes, Aaron M.; Govendir, Merran
• Is Part Of: Journal of veterinary pharmacology and therapeutics. Volume 43:Issue 2(2020)
• Page Start: 115
• Page End: 122
• Publication Date: 2019-06-10
• Subjects: amoxicillin -- koala -- metabolite -- pharmacokinetic -- Phascolarctos cinereus; Veterinary pharmacology -- Periodicals; Therapeutics -- Periodicals; 636.0895105
• DOI: 10.1111/jvp.12767
• Languages: English
• ISSNs: 0140-7783

Abstract

Abstract: Amoxicillin was administered as a single subcutaneous injection at 12.5 mg/kg to four koalas and changes in amoxicillin plasma concentrations over 24 hr were quantified. Amoxicillin had a relatively low average ± SD maximum plasma concentration ( C max ) of 1.72 ± 0.47 µg/ml; at an average ± SD time to reach C max ( T max ) of 2.25 ± 1.26 hr, and an elimination half‐life of 4.38 ± 2.40 hr. The pharmacokinetic profile indicated relatively poor subcutaneous absorption. A metabolite was also identified, likely associated with glucuronic acid conjugation. Bacterial growth inhibition assays demonstrated that all plasma samples other than t = 0 hr, inhibited the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 to some extent. Calculated pharmacokinetic indices were used to predict whether this dose could attain a plasma concentration to inhibit some susceptible Gram‐negative and Gram‐positive pathogens. It was predicted that a twice daily dose of 12.5 mg/kg would be efficacious to inhibit susceptible bacteria with an amoxicillin minimum inhibitory concentration (MIC) ≤ 0.75 µg/ml such as susceptible Bordetella bronchiseptica, E. coli, Staphylococcus spp. and Streptococcus spp. pathogens.