NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2022, Vol. 34 ›› Issue (11): 1811-1821.doi: 10.16333/j.1001-6880.2022.11.001

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Pharmacokinetics and tissue distribution of p-hydroxybenzoic acid and sodium p-hydroxybenzoate in mice and cynomolgus monkeys

YANG Ying-ying1,WEI Cheng-qiong1,WEI Xing-shu1,WANG Yu-hui1*,DUAN Xiao-qun2*   

  1. 1School of Pharmacy,Guilin Medical University;2School of Biomedical in Dustry,Guilin Medical University,Guilin 541199,China
  • Online:2022-11-25 Published:2022-11-25

Abstract:

Previous studies have shown that p-hydroxybenzoic acid (p-HBA) and sodium p-hydroxybenzoate (s-HBA) are both potential drugs for the treatment of ulcerative colitis.In this study,the pharmacokinetic and tissue distribution characteristics of p-HBA and s-HBA were studied in normal mice and cynomolgus monkeys after a single administration of s-HBA.Mice were given 20 mg/kg p-HBA and 20,50 and 100 mg/kg s-HBA by intragastric administration,and cynomolgus monkeys were given 4,10,and 20 mg/kg s-HBA by intragastric administration.The concentrations of p-HBA and s-HBA in plasma and tissue of mice and s-HBA in plasma of cynomolgus monkeys were determined by LC-MS/MS.All plasma and tissue samples were treated with acetonitrile precipitated protein method.At the dose of 20 mg/kg,Tmax of p-HBA and s-HBA was 0.08 and 0.08 h,Cmax of plasma was 20 453.98 and 30 683.33 ng/kg,and AUC0-t was 7 180.27 and 12 008.42 ng·h/mL,t1/2 was 0.57 and 0.59 h,respectively.The Cmax and AUC0-t showed a good linear relationship with dose of s-HBA in mice and cynomolgus monkeys.The high concentration of p-HBA can be detected in the tissues of heart,liver,spleen,lung,kidney,brain and colon of mice after administration of p-HBA and s-HBA.The results showed that p-HBA and s-HBA were quickly absorbed and eliminated in mice and cynomolgus monkeys after oral administration,and were widely distributed in mice tissues,with the highest concentration in kidney and liver.It was speculated that p-HBA had certain targeting property on kidney and liver,and there was no obvious accumulation in all tissues,prompting its good security.

Key words: p-hydroxybenzoic acid, sodium p-hydroxybenzoate, LC-MS/MS, pharmacokinetics, tissue distribution, cynomolgus monkeys

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