Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction

Clin Pharmacol Ther. 2000 Oct;68(4):345-55. doi: 10.1067/mcp.2000.109797.


Background: P-Glycoprotein is an efflux pump in many epithelial cells with excretory function. It has been demonstrated that rifampin (INN, rifampicin) induces P-glycoprotein, particularly in the gut wall. We therefore hypothesized that rifampin affects pharmacokinetics of the P-glycoprotein substrate talinolol, a beta1-blocker without appreciable metabolic disposition but intense intestinal secretion in human beings.

Methods: Pharmacokinetics of talinolol (a single dose of 30 mg administered intravenously or 100 mg administered orally for 7 days) and duodenal expression of the MDR1 gene product P-glycoprotein as assessed by reverse transcriptase-polymerase chain reaction of the MDR1-messenger ribonucleic acid, by immunohistochemistry and Western blot analysis were analyzed before and after coadministration of rifampin (600 mg per day for 9 days) in 8 male healthy volunteers (age 22 to 26 years).

Results: During rifampin treatment, the areas under the curve of intravenous and oral talinolol were significantly lower (21% and 35%; P < .05). Treatment with rifampin resulted in a significantly increased expression of duodenal P-glycoprotein content 4.2-fold (2.9, 6.51) (Western blot) and messenger RNA was increased in six of the eight volunteers. P-Glycoprotein expression in biopsy specimens of gut mucosa correlated significantly with the systemic clearance of intravenous talinolol (rs = 0.74; P < .001).

Conclusions: Rifampin induces P-glycoprotein-mediated excretion of talinolol predominantly in the gut wall. Moreover, clearance of talinolol from the blood into the lumen of the gastrointestinal tract may be predicted by the individual intestinal P-glycoprotein expression. Thus we describe a new type of steady-state drug interaction affecting compounds that are subject to transport rather than metabolism.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Administration, Oral
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / blood
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Adult
  • Anti-Arrhythmia Agents / pharmacokinetics
  • Antihypertensive Agents / pharmacokinetics
  • Antitubercular Agents / pharmacology*
  • Area Under Curve
  • Blotting, Western
  • Duodenum / metabolism*
  • Endoscopy, Digestive System
  • Enzyme Induction / drug effects
  • Humans
  • Immunohistochemistry
  • Infusions, Intravenous
  • Male
  • Propanolamines / administration & dosage
  • Propanolamines / blood
  • Propanolamines / pharmacokinetics*
  • RNA, Messenger / analysis
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rifampin / pharmacology*
  • Up-Regulation


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Antihypertensive Agents
  • Antitubercular Agents
  • Propanolamines
  • RNA, Messenger
  • talinolol
  • Rifampin