The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron

Clin Pharmacol Ther. 1999 Apr;65(4):377-81. doi: 10.1016/S0009-9236(99)70130-X.


Background: Ondansetron is an antiemetic agent metabolized by cytochrome P450 (CYP) enzymes. Rifampin (INN, rifampicin) is a potent inducer of CYP3A4 and some other CYP enzymes. We examined the possible effect of rifampin on the pharmacokinetics of orally and intravenously administered ondansetron.

Methods: In a randomized crossover study with 4 phases and a washout of 4 weeks, 10 healthy volunteers took either 600 mg rifampin (in 2 phases) or placebo (in 2 phases) once a day for 5 days. On day 6, 8 mg ondansetron was administered either orally (after rifampin and placebo) or intravenously (after rifampin and placebo). Ondansetron concentrations in plasma were measured up to 12 hours.

Results: The mean total area under the plasma concentration-time curve [AUC(0-infinity)] of orally administered ondansetron after rifampin pretreatment was reduced by 65% compared with placebo (P < .001). Rifampin decreased the peak plasma concentration of oral ondansetron by about 50% (from 27.2+/-3.0 to 13.8+/-1.5 ng/mL [mean +/- SEM]; P < .001]) and the elimination half-life (t1/2) by 38% (P < .01). The bioavailability of oral ondansetron was reduced from 60% to 40% (P < .01) by rifampin. The clearance of intravenous ondansetron was increased 83% (from 440+/-38.4 to 805+/-44.6 mL/min [P < .001]) by rifampin. Rifampin reduced the t1/2 of intravenously administered ondansetron by 46% (P < .001) and the AUC(0-infinity) by 48% (P < .001).

Conclusions: Rifampin considerably decreases the plasma concentrations of ondansetron after both oral and intravenous administration. The interaction is most likely the result of induction of the CYP3A4-mediated metabolism of ondansetron. Concomitant use of rifampin or other potent inducers of CYP3A4 with ondansetron may result in a reduced antiemetic effect, particularly after oral administration of ondansetron.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Antiemetics / administration & dosage*
  • Antiemetics / blood
  • Antiemetics / pharmacokinetics*
  • Cross-Over Studies
  • Cytochrome P-450 Enzyme Inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Ondansetron / administration & dosage*
  • Ondansetron / blood
  • Ondansetron / pharmacokinetics*
  • Rifampin / pharmacology*


  • Antiemetics
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Ondansetron
  • Rifampin