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Ocular and systemic pharmacokinetics of lidocaine hydrochloride ophthalmic gel in rabbits after topical ocular administration

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Abstract

Lidocaine hydrochloride ophthalmic gel is a novel ophthalmic preparation for topical ocular anesthesia. The study is aimed at evaluating the ocular and systemic pharmacokinetics of lidocaine hydrochloride 3.5 % ophthalmic gel in rabbits after ocular topical administration. Thirty-six rabbits were randomly placed in 12 groups (3 rabbits per group). The rabbits were quickly killed according to their groups at 0 (predose), 0.0833, 0.167, 0.333, 0.667, 1, 1.5, 2, 3, 4, 6, and 8 h postdose and then the ocular tissue and plasma samples were collected. All the samples were analyzed by a validated LC–MS/MS method. The test result showed that the maximum concentration (C max) of lidocaine in different ocular tissues and plasma were all achieved within 20 min after drug administration, and the data of C max were (2,987 ± 1814) μg/g, (44.67 ± 12.91) μg/g, (26.26 ± 7.19) μg/g, (11,046 ± 2,734) ng/mL, and (160.3 ± 61.0) ng/mL for tear fluid, cornea, conjunctiva, aqueous humor, and plasma, respectively. The data of the elimination half-life in these tissues were 1.5, 3.2, 3.5, 1.9, and 1.7 h for tear fluid, cornea, conjunctiva, aqueous humor, and plasma, respectively. The intraocular lidocaine levels were significantly higher than that in plasma, and the elimination half-life of lidocaine in cornea, conjunctiva, and aqueous humor was relatively longer than that in tear fluid and plasma. The high intraocular penetration, low systemic exposure, and long duration in the ocular tissues suggested lidocaine hydrochloride 3.5 % ophthalmic gel as an effective local anesthetic for ocular anesthesia during ophthalmic procedures.

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Acknowledgments

All authors participated in the analysis and interpretation of data and in the writing of the manuscript, and approved the final manuscript. The authors thank the team at Centre for New Drug Safety Evaluation and Research of China Pharmaceutical University for conducting the study.

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Authors and Affiliations

  1. Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China

    Bing Liu, Li Ding, Xiaowen Xu, Hongda Lin & Chenglong Sun

  2. Centre for New Drug Safety Evaluation and Research, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, China

    Linjun You

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  1. Bing Liu
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  2. Li Ding
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  3. Xiaowen Xu
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  4. Hongda Lin
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Correspondence to Li Ding.

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Liu, B., Ding, L., Xu, X. et al. Ocular and systemic pharmacokinetics of lidocaine hydrochloride ophthalmic gel in rabbits after topical ocular administration. Eur J Drug Metab Pharmacokinet 40, 409–415 (2015). https://doi.org/10.1007/s13318-014-0218-5

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  • DOI: https://doi.org/10.1007/s13318-014-0218-5

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