Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite

Clin Pharmacol Ther. 2009 Jan;85(1):78-85. doi: 10.1038/clpt.2008.186. Epub 2008 Oct 8.


The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Infective Agents / pharmacology*
  • Area Under Curve
  • Blood Glucose / drug effects*
  • Ciprofloxacin / pharmacology*
  • Drug Interactions
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Glyburide / metabolism
  • Glyburide / pharmacokinetics*
  • Humans
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacokinetics*
  • Infusions, Intravenous
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Liver-Specific Organic Anion Transporter 1 / drug effects*
  • Male
  • Metabolic Clearance Rate
  • Rifampin / administration & dosage
  • Rifampin / pharmacology*


  • Anti-Infective Agents
  • Blood Glucose
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Liver-Specific Organic Anion Transporter 1
  • Ciprofloxacin
  • Glyburide
  • Rifampin