title: Pharmacokinetics of cisplatin in the absence or presence of zengmian yiliu granules (a traditional Chinese medicine compound) in rats determined via ICP-MS: an investigation on drug-herb interactions.
abstract: BACKGROUND
  Cisplatin is a highly effective chemotherapeutic agent against many tumors; however, it has potent adverse effects. Zengmian Yiliu granule (ZMYL), a traditional Chinese medicine (TCM) compound, has been clinically used against platinum (Pt)-induced toxicity and to enhance the efficacy of cisplatin.
  
  
  OBJECTIVE
  The study was conducted to investigate the likelihood of potential pharmacokinetics drug-herbs interaction (DHI) between cisplatin and ZMYL.
  
  
  METHODS
  An improved ICP-MS method combined with ultrafiltration and microwave-assisted digestion was performed to determine the total and free Pt concentrations in rat plasma after intraperitoneal administration of cisplatin (9 mg/kg) or a combined administration with ZMYL (1 g/kg) by gavage.
  
  
  RESULTS
  ZMYL produced a potential DHI on the pharmacokinetic parameters of cisplatin, calculated from the total Pt concentration. The clearance rate decreased from 110.52 to 66.12 mLh(-1 )kg(-1), the mean residence time extended from 63.1 to 164.54 h, the area under the plasma concentration-time curve increased from 86.58 to 152.93 µg h mL(-1), the elimination half-life extended from 48.38 to 126.4 h, and the elimination rate constant decreased from 0.017 to 0.006 h, in the ZMYL combination group (p < 0.05). In terms of free Pt concentration, the apparent volume of distribution and clearance rate was statistically different (p < 0.05). The Pt plasma protein binding ratios in the early dose stages were significantly boosted by the co-administration of ZMYL (p < 0.01).
  
  
  CONCLUSIONS
  ZMYL is a potential complementary and alternative medicine for cisplatin chemotherapy. The therapeutic benefits of ZMYL-cisplatin chemotherapy derived from pharmacokinetic interaction needs further investigation.
authors.affiliation: Department of Gynaecology, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine , Shanghai , PR China .
authors.forename: Qin-Hua
authors.initials: QH
authors.lastname: Zhang
authors.forename: Can
authors.initials: C
authors.lastname: Gong
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Hai
authors.initials: H
authors.lastname: Wei
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Zhou
authors.forename: Cong
authors.initials: C
authors.lastname: Qi
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D041743:Herb-Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D013058:Mass Spectrometry; D008516:Medicine, Chinese Traditional; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D014462:Ultrafiltration
chemical_list: D004365:Drugs, Chinese Herbal; C000601926:zengmian yiliu; D002945:Cisplatin
keywords: Drug combination; free platinum; total platinum