Population pharmacokinetics and penetration into prostatic, seminal, and vaginal fluid for ciprofloxacin, levofloxacin, and their combination

Chemotherapy. 2011;57(5):402-16. doi: 10.1159/000329520. Epub 2011 Oct 18.

Abstract

Background: Our objectives were to assess the pharmacokinetic interaction and body fluid penetration of ciprofloxacin and levofloxacin.

Methods: This study was a single-dose open randomized three-way crossover in 15 healthy volunteers receiving 500 mg oral levofloxacin, 500 mg oral ciprofloxacin, or 250 mg levofloxacin and 250 mg ciprofloxacin co-administered. Serum, urine, and body fluid concentrations were determined by high-performance liquid chromatography and analyzed via population pharmacokinetic modeling.

Results: Modeling indicated that ciprofloxacin inhibited the renal reabsorption of levofloxacin. Ciprofloxacin increased the net renal clearance of levofloxacin by 13%, as its estimated affinity for a putative tubular reabsorption transporter was 12-fold higher (Km: 568 μM) compared to levofloxacin (Km: 6,830 μM). Levofloxacin increased the bioavailability of ciprofloxacin by 12% and achieved significantly (p < 0.05) higher concentrations at 3 h in ejaculate, prostatic, seminal, and vaginal fluid compared to ciprofloxacin.

Conclusion: Modeling suggested that ciprofloxacin inhibited the tubular reabsorption of levofloxacin due to a 12-fold higher affinity for a putative tubular reabsorption transporter compared to levofloxacin. This pharmacokinetic interaction was not clinically relevant.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Body Fluids / drug effects
  • Body Fluids / metabolism*
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacokinetics*
  • Cross-Over Studies
  • Drug Combinations
  • Drug Interactions
  • Female
  • Humans
  • Levofloxacin*
  • Male
  • Ofloxacin / administration & dosage
  • Ofloxacin / pharmacokinetics*
  • Prostate / drug effects
  • Prostate / metabolism*
  • Semen / drug effects
  • Semen / metabolism
  • Seminal Vesicles / drug effects
  • Seminal Vesicles / metabolism*
  • Tissue Distribution / drug effects
  • Tissue Distribution / physiology
  • Vagina / drug effects
  • Vagina / metabolism*
  • Young Adult

Substances

  • Drug Combinations
  • Ciprofloxacin
  • Levofloxacin
  • Ofloxacin