Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination

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.

The Effectiveness of Single-Dose Fosfomycin as Antimicrobial Prophylaxis for Patients Undergoing Transrectal Ultrasound-Guided Biopsy of the Prostate

“…Interestingly, there was no FREc in the levofloxacin group, but in the ciprofloxacin group, 7/14 patients showed FREc. We believe that this difference occurred because levofloxacin penetrates better to the prostate than ciprofloxacin, as recently reported by Bulitta et al [24] . The choice of fosfomycin as the agent to be included in the study was based on numerous published data reporting that E. coli is the most common organism implicated in post-biopsy infection and that the 90% of Enterobacteriaceae isolates with advanced resistance to antimicrobial drugs are susceptible to fosfomycin [11] .…”

Quantitative analysis of endogenous compounds

“…However, by definition, analyte-free biological matrices do not exist for endogenous compounds. Furthermore, blank matrices may not be available or can be difficult to obtain, even for some exogenous compounds, because they are rare matrices such as tears, seminal, and vaginal fluid [22,23], or due to contamination with analytes such as antibiotics in wastewaters [24], or presence of identical matrix components with the same MS and chromatography properties as the analytes of interest such as erlotinib [25].…”

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

“…LEV presents a low level of protein binding (24% to 38%) in humans and readily distributes throughout the body, with a mean volume of distribution (V) of 1.1 liters/kg of body weight (11). Biopsy studies have indicated that LEV has a high level of prostate penetration (12,13) and lung penetration (14). However, measurements from tissue homogenates can overestimate drug concentrations at the target site, especially for fluoroquinolones that accumulate in the intracellular space (15).…”