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Oral Bioavailability and Mass Balance Studies of a Novel Anti-arrhythmic Agent Sulcardine Sulfate in Sprague–Dawley Rats and Beagle Dogs

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Abstract

Background and Objectives

Sulcardine sulfate is a newly developed candidate drug used to control arrhythmias. The aim of this research was to investigate the pharmacokinetics, bioavailability and excretion characteristics of sulcardine in animals.

Methods

Sprague–Dawley rats were orally and intravenously given sulcardine at 20 and 40 mg/kg. Beagle dogs were also orally and intravenously dosed at 10 mg/kg. Both [3H]-labeled sulcardine and unlabeled sulcardine were given to rats. Feces, urine and bile were collected at 0–72 h for mass balance study. The contents of unlabeled sulcardine and radioactivity in samples were determined by a validated LC–MS/MS method and by liquid scintillation counting, separately.

Results

Sulcardine was rapidly eliminated in rats after dosing. The oral bioavailability was 34–35 % in rats, while a higher exposure was observed in dogs (bioavailability = 62.7 %). More than 90 % of dosed sulcardine was recovered, and approximately 20–40 % of the dose excreted into urine as the original form, and the remaining was found in feces and bile, most of which (about 40 %) was transformed into metabolites. No difference was observed between sexes. Metabolism may occur to a large extent after oral administration in rats but to a smaller extent in dogs.

Conclusions

Sulcardine was extensively absorbed in both rats and dogs after oral administration. The mass balance data indicated that sulcardine was widely metabolized in rats after oral administration.

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References

  1. Li LQ, Qu ZX, Wang ZM, Zeng YL, Ding GS, Hu GJ, et al. Studies on a new antiarrhythmic drug changrolin-4-(3′,5′-bis [(N-pyrrolidinyl) methyl]-4′-hydroxyanilino)-quinazoline. Sci Sin. 1979;22:1220–8.

    CAS  PubMed  Google Scholar 

  2. Lu LL, Habuchi YJ, Tanaka H, Morikawa J. Electrophysiological effects of changrolin, an anti-arrhythmic agent derived from Dichroa febrifuga, on guinea-pig and rabbit heart cells. Clin Exp Pharmacol Physiol. 1995;22:337–41.

    Article  CAS  PubMed  Google Scholar 

  3. Chen WH, Wang WY, Zhang J, Yang D, Wang YP. State-dependent blockade of human ether-a-go-go-related gene (herg) k(+) channels by changrolin in stably transfected hek293 cells. Acta Pharmacol Sin. 2010;31:915–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Qu ZX, Cao CY, Zhuang YH. The effects of infusion rate of Changrolin on drug concentration in blood and ECG (author’s transl). Yao Xue Xue Bao. 1980;15:449–55 (Chinese).

    CAS  PubMed  Google Scholar 

  5. Bai DL, Chen WZ, Bu YX, Wang YP, Dong YL, Kang AL. N-substituted benzyl or phenyl aromatic sulfamides compounds and the use thereof. US Patent 6605635B1. 2003 Aug 12.

  6. Bai DL, Chen WZ, Bu YX, Dong YL, Kang AL, Sun WK, et al. Discovery of -(3,5-bis(1-pyrrolidylmethyl)-4-hydroxybenzyl)-4-methoxybenzenesulfamide (sulcardine) as a novel anti-arrhythmic agent. Acta Pharmacol Sin. 2012;33:1176–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324:781–8.

    Article  CAS  PubMed  Google Scholar 

  8. Yang D, Yu C, Li SJ, Liu GY, Lu YL, Wang YP. Liquid chromatography/tandem mass spectrometry for the determination of changrolin in rat plasma: application to a bioavailability study. J Pharm Biomed Anal. 2009;50:189–93.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan – Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China

    You-li Lu, Shui-jun Li, Gang-yi Liu, Jing-ying Jia, Meng-qi Zhang, Hong-chao Zheng, Chen Yu & Fu Zhu

  2. Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China

    Xiao-chuan Li & Yi-ping Wang

  3. Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China

    Ding Yang

Authors
  1. You-li Lu
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  2. Shui-jun Li
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  3. Gang-yi Liu
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  4. Xiao-chuan Li
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  5. Ding Yang
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  6. Jing-ying Jia
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  8. Hong-chao Zheng
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  9. Chen Yu
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  10. Fu Zhu
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  11. Yi-ping Wang
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Corresponding author

Correspondence to Yi-ping Wang.

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Funding

This work was supported by grants from the Ministry of Science and Technology of China (No.2010ZX09502-003), and the Shanghai Committee of Science and Technology, China (No. 15DZ2291800).

Conflict of interest

All of the authors, You-li Lu, Shui-jun Li, Gang-yi Liu, Xiao-chuan Li, Ding Yang, Jing-ying Jia, Meng-qi Zhang, Hong-chao Zheng, Chen Yu, Fu Zhu, Yi-ping Wang declare no conflict of interest.

Ethical approval

The animal experiments were conducted according to approval of Institutional Animal Care and Use Committee. All applicable international, national and/or institutional guidelines for the Care and Use of Laboratory Animals were followed.

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Lu, Yl., Li, Sj., Liu, Gy. et al. Oral Bioavailability and Mass Balance Studies of a Novel Anti-arrhythmic Agent Sulcardine Sulfate in Sprague–Dawley Rats and Beagle Dogs. Eur J Drug Metab Pharmacokinet 42, 453–459 (2017). https://doi.org/10.1007/s13318-016-0360-3

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  • DOI: https://doi.org/10.1007/s13318-016-0360-3

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