Concentrations of moxifloxacin in plasma and urine, and penetration into prostatic fluid and ejaculate, following single oral administration of 400mg to healthy volunteers

Wagenlehner, F.; Kees, Frieder; Weidner, W.; Wagenlehner, C.; Naber, Kurt G.

doi:10.1016/j.ijantimicag.2007.08.025

Cited by 46 publications

(45 citation statements)

References 35 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, increased eradication of Enterococci was observed in the Cipro-750 cohort. As mentioned above, the distribution of ciprofloxacin to prostatic secretions is suboptimal, reaching, for example, the concentration of 0.18 mg l 21 after a single dose of 400 mg. 17 For this reason, ciprofloxacin may not have been active on a number of enterococcal isolates exposed to a daily 500-mg dose of the quinolone, as Enterococcus isolates in complicated urinary tract infections mostly show minimum inhibitory concentrations above 0.5 mg l 21 (for example, see Ref. 30).…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15] For these reasons, current pharmacological research in the field of bacterial prostatitis also focuses on the investigation of new prostatotropic antibacterials or on the optimisation of dosages and combinations of available antibiotics. 16,17 We previously reported the outcome of a 6-week combination therapy protocol administered to CBP patients that was based on a single 500-mg daily dose of ciprofloxacin (cumulative dose: 21 g) and a thrice-weekly 500-mg dose of azithromycin. 18 Although treatment was effective and well tolerated, patients described the treatment as lengthy and difficult to comply with.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

Magri¹,

Montanari²,

Škerk³

et al. 2011

Asian J Androl

View full text Add to dashboard Cite

We previously demonstrated the safety and efficacy of fluoroquinolone-macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500-or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week 21 ) with ciprofloxacin at the rate of 750 mg day 21 for 4 weeks rather than at 500 mg day 21 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone-macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

Magri¹,

Montanari²,

Škerk³

et al. 2011

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…The potential role of ion trapping may be considered not only by relating drug concentrations in plasma and tissue but also by taking into account potential differences in pH between plasma and tissue, under the given set of circumstances. For example, moxifloxacin has been shown to accumulate in prostatic secretions in healthy subjects, with a prostatic secretion-toplasma ratio of 1.57 (152). In this scenario, as minimal differences have been observed between plasma and prostatic secretion pH in healthy subjects (153), it is unlikely that ion trapping explains the observations, but rather, differences in lipophilicty, binding to cellular matrices, and/or rapid cellular uptake/release kinetics may play a role (154).…”

Section: In Vivo Studiesmentioning

confidence: 99%

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

2013

View full text Add to dashboard Cite

SUMMARY For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection.

show abstract

“…Studies based on prostatic fluid concentrations have shown that newer generation quinolones such as gatifloxacin and moxifloxacin are able to penetrate into the prostate tissue to a more significant extent compared to older quinolones and to other antimicrobial agents such as ␤-lactams and cephalosporins (5,6). It has been reported that levofloxacin, a broad-spectrum fluoroquinolone that was approved in the United States for the treatment of bacterial prostatitis in 2003, has a good distribution into prostatic fluid and ejaculate (7)(8)(9).…”

mentioning

confidence: 99%

Population Pharmacokinetic Modeling of the Unbound Levofloxacin Concentrations in Rat Plasma and Prostate Tissue Measured by Microdialysis

Hurtado

Weber

Derendorf

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bLevofloxacin is a broad-spectrum fluoroquinolone used in the treatment of both acute and chronic bacterial prostatitis. Currently, the treatment of bacterial prostatitis is still difficult, especially due to the poor distribution of many antimicrobials into the prostate, thus preventing the drug to reach effective interstitial concentrations at the infection site. Newer fluoroquinolones show a greater penetration into the prostate. In the present study, we compared the unbound levofloxacin prostate concentrations measured by microdialysis to those in plasma after a 7-mg/kg intravenous bolus dose to Wistar rats. Plasma and dialysate samples were analyzed using a validated high-pressure liquid chromatography-fluorescence method. Both noncompartmental analysis (NCA) and population-based compartmental modeling (NONMEM 6) were performed. Unbound prostate tissue concentrations represented 78% of unbound plasma levels over a period of 12 h by comparing the extent of exposure (unbound AUC 0 -ؕ ) of 6.4 and 4.8 h·g/ml in plasma and tissue, respectively. A three-compartment model with simultaneous passive diffusion and saturable distribution kinetics from the prostate to the central compartment gave the best results in terms of curve fitting, precision of parameter estimates, and model stability.

show abstract

Concentrations of moxifloxacin in plasma and urine, and penetration into prostatic fluid and ejaculate, following single oral administration of 400mg to healthy volunteers

Cited by 46 publications

References 35 publications

Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

Population Pharmacokinetic Modeling of the Unbound Levofloxacin Concentrations in Rat Plasma and Prostate Tissue Measured by Microdialysis

Contact Info

Product

Resources

About