title: In vitro and in vivo evaluation of the effects of duloxetine on P-gp function.
abstract: OBJECTIVE
  To evaluate the effect of duloxetine (DLX) on the P-glycoprotein (P-gp) function in vitro and in vivo.
  
  
  METHODS
  In vitro experiment was conducted using the Caco-2 cell, a human colon cancer cell line that naturally expresses the P-gp and P-gp function was evaluated by monitoring whether DLX affect the accumulation of Rhd123. In vivo study was conducted by quantitating the effect of orally administered DLX on the bioavailability of talinolol.
  
  
  RESULTS
  In the in vitro study, incubation of Caco-2 cell with DLX caused a concentration-dependent increase in the accumulation of Rhd123. In the in vivo study, co-administration of DLX increased the bioavailability of talinolol. The ratio (90% confidence intervals) of AUC(0-60), AUC(0-∞), and C(max) (talinolol alone versus talinolol plus DLX) were 0.87(0.77-1.06), 0.85(0.74-1.01), 0.87 (0.68-1.12).
  
  
  CONCLUSIONS
  Our results suggest that DLX could inhibit the function of P-gp in vitro and in vivo, and caution should be exercised when DLX is to be co-administered with drugs that are P-gp substrate.
authors.affiliation: Clinical Pharmacy Research Institute, The Second Xiangya Hospital, Central South University, Changsha, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Ruike
authors.forename: Cao
authors.initials: C
authors.lastname: Junhua
authors.forename: Peng
authors.initials: P
authors.lastname: Wenxing
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D000928:Antidepressive Agents / Q000378:metabolism / Q000494:pharmacology*; D018938:Caco-2 Cells; D004347:Drug Interactions; D004351:Drug Resistance; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011412:Propanolamines; D013876:Thiophenes; C011550:talinolol; D000068736:Duloxetine Hydrochloride