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Xenobiotica
the fate of foreign compounds in biological systems
Volume 50, 2020 - Issue 12
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Animal Pharmacokinetics and Metabolism

Comparative analysis of pharmacokinetics of vancomycin hydrochloride in rabbits after ocular, intragastric, and intravenous administration by LC-MS/MS

, , , , , , & show all
Pages 1461-1468 | Received 06 Apr 2020, Accepted 22 May 2020, Published online: 04 Jun 2020
 

Abstract

  1. The objective of this study was to compare the pharmacokinetics of vancomycin hydrochloride administered into rabbits through different routes and explore the feasibility of peptide drugs entering the systemic circulation through ocular administration.

  2. A convenient, accurate, and rapid liquid chromatography-trandem mass spectrometric (LC-MS/MS) method was established and used for the determination of vancomycin hydrochloride in rabbit plasma after intravenous administration (1.5 mg/kg), intragastric, and ocular administration (15 mg/kg). The pharmacokinetic parameters were analyzed using the DAS 2.0 software.

  3. We obtained a linear calibration curves vancomycin hydrochloride in plasma of rabbits over a concentration range of 0.05–10.0 μg/mL (R2 > 0.9995), the interassay accuracy was within 5%, precision of 1.66–3.38%, and recovery of >85%. No matrix effects were observed. The absolute bioavailability of vancomycin hydrochloride after intragastric and ocular administration was 1.0 and 7.3%, with the half-life values of 63.1 and 138.5 min, respectively.

  4. Therefore, the LC-MS/MS method established in this experiment was suitable for the determination of vancomycin hydrochloride. Vancomycin hydrochloride was rapidly absorbed into the blood circulation after ocular administration. Ocular administration was linked to higher bioavailability compared with intragastric administration, suggesting that the former will become a route for the delivery of peptide drugs.

Acknowledgments

All of the authors acknowledge that this study was supported by the Natural Science Foundation in Higher Education of Anhui Province (KJ2019A0454; Anhui Province “Special Support Plan” for the Second Batch of Innovative Leading Talents).

Disclosure statement

The authors declare that they have no other conflict of financial interests.

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