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Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4-Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass Spectrometry

  • Jia Hui Wang
  • Song Hui Hu
  • Ji Yan Su
  • Jun Ping Pan
  • Xiang Nan Mi
  • Hai Ju Geng
  • Wei Zhang
  • Liang Cai
  • Chao Fen Su
  • Ai Hua Hong
  • Huan Min LuoEmail author
Original Research Article

Abstract

Background and Objectives

Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the pharmacokinetics and tissue distribution characteristics of MDHB.

Methods

The pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS after a single intragastric administration (50 to 450 mg/kg) in mice, and samples were collected from five animals at specific time points.

Results

Pharmacokinetic parameters of MDHB following intragastric administrations were: the time to peak concentration (Tmax) ranged from 0.033 to 0.07 h, the peak concentration (Cmax) ranged from 12,379.158 to 109798.712 μg/l, the elimination half-life (t1/2z) ranged from 0.153 to 1.291 h, the area under the curve (AUC0–∞) ranged from 640.654 to 20,241.081 μg/l × h, the mean residence time (MRT0–∞) ranged from 0.071 to 0.206 h, the apparent volume of distribution (Vz/F) ranged from 17.538 to 45.244 l/kg, and the systemic clearance (Clz/F) ranged from 22.541 to 80.807 l/h/kg. The oral bioavailability of MDHB was 23%. The maximum MDHB content was detected in the stomach, and the minimum content was observed in the testes; the peak content in the brain was 15,666.93 ng/g.

Conclusions

The pharmacokinetic characteristics of MDHB include fast absorption, high systemic clearance, a short half-life and an oral bioavailability of 23%. Additionally, MDHB permeates the blood-brain barrier (BBB) and is rapidly distributed to all organs. The identification of the pharmacokinetics of MDHB following its oral administration will contribute to further preclinical and clinical studies of its effects.

Notes

Compliance with Ethical Standards

Funding

This work was supported by grants from the National Natural Science Foundation Committee of China (grant nos. 81473296, 81173037 and 81202519), the National Program on Key Basic Research Project (973 Program; no. 2011CB707500) and the Guangdong Provincial Department of Science and Technology (grant nos. 2012B050300018 and 2010B030700018).

Conflict of Interest

None of the authors have conflicts of interest to declare.

Ethical Approval

The animal experiments adhered to the “Jinan University Medical College Animal Use Ordinance” and were approved by the Ethics Committee of the Medical School of Jinan University.

Supplementary material

13318_2018_512_MOESM1_ESM.docx (906 kb)
Supplementary material 1 (DOCX 905 kb)

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Pharmacology, School of MedicineJinan UniversityGuangzhouChina
  2. 2.State Key Laboratory of Applied Microbiology Southern ChinaGuangdong Institute of MicrobiologyGuangzhouChina
  3. 3.School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhouChina
  4. 4.Department of Pathogen Biology and Medical Immunology, School of Basic MedicineNingxia Medical UniversityYinchuanChina
  5. 5.School of International EducationAnhui Medical UniversityHefeiChina
  6. 6.Analytical and Testing Center, Jinan UniversityGuangzhouChina
  7. 7.Institute of Brain SciencesJinan UniversityGuangzhouChina

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