Distribution and antimicrobial activity of ciprofloxacin in human soft tissues

Abstract

Interstitial ciprofloxacin concentrations in soft tissues were measured by microdialysis following intravenous administration of 200 mg to each of eight healthy volunteers. Interstitial ciprofloxacin concentrations were significantly lower than corresponding total serum drug concentrations; the interstitium-to-serum concentration ratios ranged from 0.55 to 0.73. An in vitro simulation based on interstitial pharmacokinetics showed a substantially lower antimicrobial activity than did the simulation based on serum pharmacokinetics. Thus, ciprofloxacin concentrations at the site of effect may be subinhibitory although effective concentrations are attained in serum.

FIG. 1

Time-concentration profiles for drug concentrations in total serum and interstitial space fluids of skeletal muscle and subcutaneous adipose tissue following administration of ciprofloxacin to healthy volunteers (single intravenous dose of 200 mg administered over 10 min; n = 8). Results are presented as means ± SEs. 0 to 10 min, time of administration.

FIG. 2

Mean time-kill curves for the in vitro simulation model, in which the in vivo time course of ciprofloxacin concentration, obtained by measuring antibiotic concentrations in serum and the interstitial space fluid in the experiments shown in Fig. 1, was simulated in vitro for Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Solid symbols indicate time-kill data for serum drug concentrations; open symbols indicate time-kill data for interstitial subcutaneous concentrations; the dotted lines (small solid symbols) are the growth control curves.