title: Enhanced penetration of moxifloxacin into rat prostate tissue evidenced by microdialysis.
abstract: Moxifloxacin is reported to have increased distribution into the prostate compared with older fluoroquinolones such as norfloxacin and ciprofloxacin, being able to reach tissue-to-plasma concentration ratios greater than unity. However, most of these studies use tissue homogenates derived from biopsy samples, which can lead to overestimation of free concentrations as fluoroquinolones tend to accumulate in the intracellular space. The aim of this study was to investigate moxifloxacin pharmacokinetics in rat prostate interstitial fluid by microdialysis. Tissue pharmacokinetics was assessed by implanting a small microdialysis catheter in the prostate gland. Blood samples were simultaneously collected for assessing plasma pharmacokinetics. Analysis of plasma (N=154) and microdialysis (N=344) concentrations after a single intravenous dose of 6 or 12mg/kg moxifloxacin was conducted in the non-linear mixed-effect modelling software NONMEM v.6 as well by a non-compartmental approach. Moxifloxacin showed a significant tissue distribution in the prostate (AUCprostate,ISF/fu·AUCplasma=1.24±0.37), 59% higher than the value obtained for levofloxacin in a previous study. A three-compartment model with non-linear kinetics could adequately describe moxifloxacin pharmacokinetics in terms of curve fitting and precision in parameter estimation. The developed pharmacokinetic model indicates that passive diffusion and active transport are the mechanisms involved in moxifloxacin distribution to the prostate. These findings suggest that moxifloxacin could be a better alternative to levofloxacin for the treatment of chronic bacterial prostatitis owing to its enhanced tissue penetration and higher AUCtissue/MIC ratios, even though it is not yet approved by the US FDA for this indication.
authors.affiliation: Pharmaceutical Sciences Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: K Hurtado
authors.affiliation: Pharmaceutical Sciences Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors.forename: João Victor
authors.initials: JV
authors.lastname: Laureano
authors.affiliation: Pharmaceutical Sciences Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
authors.forename: Graziela
authors.initials: G
authors.lastname: de A Lock
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville, FL 32610, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.affiliation: Pharmaceutical Sciences Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil. Electronic address: dalla.costa@ufrgs.br.
authors.forename: Teresa
authors.initials: T
authors.lastname: Dalla Costa
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D015233:Models, Statistical; D000077266:Moxifloxacin; D010949:Plasma / Q000737:chemistry; D011467:Prostate / Q000737:chemistry*; D017208:Rats, Wistar; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin
keywords: Fluoroquinolones; Microdialysis; Moxifloxacin; Pharmacokinetics; Prostate