Effect of rifampin and tobacco smoking on the pharmacokinetics of ropivacaine

Clin Pharmacol Ther. 2001 Oct;70(4):344-50.


Objective: Our objective was to assess the effect of rifampin (INN, rifampicin) and tobacco smoking on the pharmacokinetics of ropivacaine.

Methods: A randomized, 2-phase, crossover study was performed in both a group of 10 healthy nonsmokers and a group of 8 healthy smokers. In both groups each subject ingested daily for 5 days either placebo or 600 mg rifampin. On day 6 each subject received intravenously over 30 minutes a single dose of 0.6 mg/kg ropivacaine. Ropivacaine, 3-hydroxyropivacaine (3-OH-ropivacaine), and (S) -2',6'-pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 hours and 24 hours, respectively. Pharmacokinetic parameters were calculated with noncompartmental methods, and t tests were used for comparisons between the phases and between the smokers and nonsmokers. The electrocardiogram was monitored for 3 hours.

Results: There were no statistically significant differences in the area under the plasma concentration-time curve (AUC), plasma clearance (CL), or half-life (t(1/2)) of ropivacaine between the smokers and nonsmokers. However, smokers excreted in urine 31% more 3-OH-ropivacaine and 62% less PPX than nonsmokers did. Rifampin decreased the AUC of ropivacaine in nonsmokers by 52% and in smokers by 38%. In nonsmokers rifampin increased the CL of ropivacaine by 93% and shortened its t(1/2) by 25%. In smokers rifampin increased the CL of ropivacaine by 47% and shortened its t(1/2) by 20%. Rifampin decreased the urinary excretion of 3-OH-ropivacaine in nonsmokers by 74% and in smokers by 68%, and it increased the excretion of PPX by 97% and 158%, respectively. No clinically significant differences in the QTc times were found between the groups or treatments.

Conclusions: Tobacco smoking increases the excretion of 3-OH-ropivacaine in urine, probably because of the increased cytochrome P450 (CYP) 1A2-mediated metabolism of ropivacaine, and decreases the excretion of CYP3A4-formed PPX in urine. Rifampin considerably increases the metabolism of ropivacaine to PPX and decreases the metabolism to 3-OH-ropivacaine in both nonsmokers and smokers.

Publication types

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

MeSH terms

  • Adult
  • Amides / administration & dosage
  • Amides / blood
  • Amides / pharmacokinetics*
  • Amides / urine
  • Anesthetics, Local / pharmacokinetics*
  • Antibiotics, Antitubercular / pharmacology*
  • Area Under Curve
  • Drug Interactions
  • Electrocardiography
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Rifampin / pharmacology*
  • Ropivacaine
  • Smoking*


  • Amides
  • Anesthetics, Local
  • Antibiotics, Antitubercular
  • Ropivacaine
  • Rifampin