title: Use status and metabolism of realgar in Chinese patent medicine.
abstract: BACKGROUND
  Realgar is widely used in combination with other herbs as Chinese patent medicine to treat a wide range of diseases in China. It is also a well known arsenical toxicant. Chronic arsenic poisoning events caused by long-term usage of realgar-containing medicines have been reported in literatures. Given to the paradoxical role of realgar, comprehensive outline of its usage status in Chinese patent medicine might provide basal data for evaluating its toxicology risks in populations. Unfortunately, the relevant information is limited. Also, a metabolic process after intake of realgar-containing medicine in humans is poorly understood.
  
  
  METHODS
  The Traditional Chinese Patent Medicine Prescription Database was reviewed to get the information on the usage status of realgar. Realgar powder was dissolved in different pH-value solutions (1, 3, 5, 7, 9 and 11) to determine the soluble arsenic concentrations from realgar. Ten volunteers aged 24-26 years old were recruited to take four pills of Niu Huang Jie Du Pian (NHJDP), a very common Chinese patent medicine with realgar, to analyze the arsenic metabolism after exposure to realgar-containing medicine. The four pills were taken according to the medical instruction. Concentrations of soluble arsenic from realgar and urinary arsenic metabolites in humans were determined by hydride generation atomic absorption spectrometry.
  
  
  RESULTS
  A total of 191 (2.25%) realgar-containing traditional Chinese patent medicines were obtained from the database, and almost 86.91% of them were for oral application. 73 (38.22%) medicines were found to be available for children. The mass fraction of arsenic in realgar-containing medicine ranged from 0.11% to 27.52%. According to medical instructions, the amount of average daily arsenic intake ranged from 0.47 to 2895.53mg. Nearly 86% medicines with daily intake of arsenic >10mg. Only inorganic arsenic (iAs) was detected from realgar in dissolution experiment and the levels of soluble iAs increased with pH values. After intake NHJDP, arsenic excretion in urine significantly increased, with a maximum excretion of iAs and monomethylarsonic acid at 6h post-ingestion and a peak excretion of dimethylarsinic acid at 9h post-ingestion. Arsenic methylation capacity was decreased after intake NHJDP. Females carried a more efficient arsenic methylation process than males.
  
  
  CONCLUSIONS
  Realgar is widely used in traditional Chinese medicine. The arsenic solubility from realgar may be enhanced under alkaline conditions. The levels of urinary arsenic metabolites significantly increased while the arsenic methylation capacity significantly decreased after intaking realgar-containing medicine, which may suggest that a potential health hazard exists if people use arsenical medicines for long-term.
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Yongfang
authors: Y
authors: Li
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Da
authors: D
authors: Wang
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Yuanyuan
authors: Y
authors: Xu
authors: Office of Disease Control and Preventive, The Fourth Affiliated Hospital of China Medical University, No. 4 Chong Shan Road, Huanggu District, Shenyang 110032, China.
authors: Boying
authors: B
authors: Liu
authors: College of Pharmacy, The Third Military Medical University, Chongqing 400038, China.
authors: Yi
authors: Y
authors: Zheng
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Boyi
authors: B
authors: Yang
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Shujun
authors: S
authors: Fan
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Xueyuan
authors: X
authors: Zhi
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China.
authors: Quanmei
authors: Q
authors: Zheng
authors: Research Center of Environment and Non-Communicable Disease, School of Public Health, China Medical University, Shenyang 110013, China. Electronic address: sungf@mail.cmu.edu.cn.
authors: Guifan
authors: G
authors: Sun
keywords: Arsenic; Arsenic methylation; Realgar; Traditional Chinese medicine.