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Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats

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Summary

The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/(kg·min), and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short (16.8 min), pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/(min·kg). In comparison, plasma concentration of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the highest concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small (0.042‰) compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite rapidly.

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Authors and Affiliations

  1. Institute of Clinic Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Ying Zhou  (周 莹), Xiao-meng He  (何晓梦), Hu-qun Li  (李虎群), Yang Ni  (倪 扬), Ming-zhen Xu  (许明珍), Hui Chen  (谌 辉) & Wei-yong Li  (黎维勇)

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  1. Ying Zhou  (周 莹)
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  2. Xiao-meng He  (何晓梦)
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  3. Hu-qun Li  (李虎群)
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  4. Yang Ni  (倪 扬)
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  5. Ming-zhen Xu  (许明珍)
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  6. Hui Chen  (谌 辉)
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  7. Wei-yong Li  (黎维勇)
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Corresponding authors

Correspondence to Hui Chen  (谌 辉) or Wei-yong Li  (黎维勇).

Additional information

This project was supported in part by the Important National Science & Technology Specific Projects in the 12th Five-year Plan of China (No. 2011ZX09302-002-01).

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Zhou, Y., He, Xm., Li, Hq. et al. Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 856–860 (2014). https://doi.org/10.1007/s11596-014-1364-3

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  • DOI: https://doi.org/10.1007/s11596-014-1364-3

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