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


CONCLUSIONS
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.
Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg, Germany.
Jurgen B
JB
Bulitta
Martina
M
Kinzig
Christoph K
CK
Naber
Florian M E
FM
Wagenlehner
Christian
C
Sauber
Cornelia B
CB
Landersdorfer
Fritz
F
Sörgel
Kurt G
KG
Naber
D000293:Adolescent; D000328:Adult; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D012661:Semen / Q000187:drug effects / Q000378:metabolism; D012669:Seminal Vesicles / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
D004338:Drug Combinations; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin