title: Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats.
abstract: BACKGROUND
  Berberine is an active alkaloid isolated from Rhizoma coptidis [Coptis chinensis Franch. (Ranunculaceae)] that is widely used for the treatment of diabetes, hyperlipidemia and hypertension. However, the pharmacokinetics of berberine in normal rats and type 2 diabetes mellitus (T2DM) model rats are not clear.
  
  
  OBJECTIVE
  This study compares the pharmacokinetics of berberine between normal and T2DM model rats.
  
  
  METHODS
  The T2DM model rats were fed with high fat diet for 4 weeks, induced by low-dose (30 mg/kg) streptozotocin for 72 h and validated by determining the peripheral blood glucose level. Rats were orally treated with berberine at a dose of 20 mg/kg and then berberine concentration in rat plasma was determined by employing a sensitive and rapid LC-MS/MS method.
  
  
  RESULTS
  The significantly different pharmacokinetic behaviour of berberine was observed between normal and T2DM model rats. When compared with the normal group, Cmax, t1/2and AUC(0-t)of berberine were significantly increased in the model group (17.35 ± 3.24 vs 34.41 ± 4.25 μg/L; 3.95 ± 1.27 vs 9.29 ± 2.75 h; 151.21 ± 23.96 vs 283.81 ± 53.92 μg/h/L, respectively). In addition, oral clearance of berberine was significantly decreased in the model group (134.73 ± 32.15 vs 62.55 ± 16.34 L/h/kg).
  
  
  CONCLUSIONS
  In T2DM model rats, the pharmacokinetic behaviour of berberine was significantly altered, which indicated that berberine dosage should be modified in T2DM patients.
authors.affiliation: a Department of Pediatrics , Yidu Central Hospital of Weifang , Shandong , China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Jia
authors.affiliation: a Department of Pediatrics , Yidu Central Hospital of Weifang , Shandong , China.
authors.forename: Binger
authors.initials: B
authors.lastname: Xu
authors.affiliation: a Department of Pediatrics , Yidu Central Hospital of Weifang , Shandong , China.
authors.forename: Jisen
authors.initials: J
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001599:Berberine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002853:Chromatography, Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D059305:Diet, High-Fat; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013311:Streptozocin; D053719:Tandem Mass Spectrometry
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D001599:Berberine; D013311:Streptozocin
keywords: Berberine; LC-MS/MS; Pharmacokinetics; T2DM