title: Blood concentration of pantoprazole sodium is significantly high in hepatogenic peptic ulcer patients, especially those with a poor CYP2C19 metabolism.
abstract: OBJECTIVE
  To determine the plasma concentration of pantoprazole sodium by high performance liquid chromatography and its distribution in patients with different CYP2C19 genotypes in an attempt to provide experimental data for the clinical dosage adjustment of the drug.
  
  
  METHODS
  Patients with liver disease and associated peptic ulcer were genotyped according to their CYP2C19 wild-type sequences and mutations in CYP2C19m1 and CYP2C19m2 by the principles of the American Surgical Association using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma concentration of pantoprazole sodium was detected after oral administration of the enteric-coated capsules in all patients. Included in the present study were 21 patients with primary liver cancer complicated by pathogenic peptic ulcers (confirmed by endoscopy), 22 patients with fatty liver and 25 healthy volunteers between January 2006 and October 2007. The subjects were administered orally with pantoprazole sodium at 40 mg/day for 1 week consecutively. The drug concentration was detected at 24 h and 1 week after drug administration by drawing 3.0 mL blood from the cubital vein.
  
  
  RESULTS
  The plasma concentration of pantoprazole sodium was related to the CYP2C19 enzyme type. The plasma concentration of extensive metabolizers (EM) was lower than that of poor metabolizers (PM) in the healthy control group at day 7 of drug administration. Regardless of PM or EM, the plasma concentration of pantoprazole sodium in primary liver cancer patients was higher than that in fatty liver patients, and even higher than that in healthy controls (P < 0.05).
  
  
  CONCLUSIONS
  These results suggest that CYP2C19 activity is inversely correlated with the severity of liver disease, especially in PM patients.
authors.affiliation: Department of Gastroenterology, Nantong No.3 People's Hospital, Nantong, Jiangsu Province, China. shaojianguo4144@yahoo.com.cn
authors.forename: Jian Guo
authors.initials: JG
authors.lastname: Shao
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.forename: Ke Qing
authors.initials: KQ
authors.lastname: Li
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Lu
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Sun
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood* / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D065731:Cytochrome P-450 CYP2C19; D005234:Fatty Liver / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077402:Pantoprazole; D010437:Peptic Ulcer / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D054328:Proton Pump Inhibitors / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19