Effect of Glycerol-Induced Acute Renal Failure on the Pharmacokinetics of Lidocaine after Transdermal Application in Rats
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- Lili Cui
- Department of Pharmacokinetics, Kyoto Pharmaceutical University
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- Shibata Nobuhito
- Department of Pharmacokinetics, Kyoto Pharmaceutical University
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- Yoshikawa Yukako
- Department of Pharmacokinetics, Kyoto Pharmaceutical University
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- Takada Kanji
- Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Abstract
In this study, the effect of glycerol-induced acute renal failure (ARF) on the pharmacokinetics of lidocaine after transdermal application was investigated in rats. Microdialysis method was applied in vitro and in vivo to the abdominal skin of rats. After topical application of 1% lidocaine, the cumulative amount of lidocaine permeated through the excised rat abdominal skin showed parallel effect between normal and ARF rats with no significant difference in the in vitro permeability coefficient of lidocaine between them, while area under the plasma concentration versus time curve of lidocaine in ARF rats increased significantly. The protein binding rate of lidocaine in ARF plasma and the blood vessel permeability to muscle tissues, assessed by β-D-glucopyranosyl fluorescein isothiocyanate-labeled (FITC) albumin, increased significantly. After intravenous infusion of 5 mg/h/kg lidocaine, both of the total body clearance and the volume of distribution of lidocaine in the ARF rats decreased significantly. These results suggested that renal dysfunction did not have any effect on the skin permeability of lidocaine, but might change the plasma protein binding of drug and blood vessel permeability which led to high plasma concentration of lidocaine.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 26 (8), 1150-1154, 2003
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204624462336
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- NII Article ID
- 110003655067
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- NII Book ID
- AA10885497
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- COI
- 1:STN:280:DC%2BD3sznslWhuw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 6620517
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- PubMed
- 12913267
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed