title: Pharmacokinetics of single- and multiple-dose oral clarithromycin in soft tissues determined by microdialysis.
abstract: The antimicrobial spectrum of clarithromycin renders this antibiotic a frequently used option in the treatment of skin and soft-tissue infections. In most cases, these infections are caused by extracellularly proliferating microorganisms. Thus, clarithromycin concentrations achieved in the interstitial space are considered particularly important for clinical efficacy. In the present study, clarithromycin concentrations in plasma and interstitial-space fluid of subcutaneous adipose tissue and skeletal muscle of six healthy male volunteers were assessed by means of the microdialysis technique after oral single-dose administration of 250 mg and multiple doses of 500 mg of clarithromycin twice a day (b.i.d.). The ratios of the area under the concentration-time curve of free clarithromycin from 0 to 24 h calculated for a single dose of 250 mg (fAUC(0-24)) in interstitial-space fluid to the fAUC(0-24) in plasma were 0.29 +/- 0.17 and 0.42 +/- 0.18 for subcutis and skeletal muscle, respectively. For 500 mg of clarithromycin at the steady state (3 to 5 days of intake twice daily), the fAUC(0-24(b.i.d.)) ratios at the steady state were 0.39 +/- 0.04 and 0.41 +/- 0.19 for subcutis and skeletal muscle, respectively. The half-life was around 2 h after a single dose but increased to approximately 4 h in plasma and tissues after repetitive clarithromycin administration. Based on subsequently performed pharmacokinetic-pharmacodynamic calculations, a dosing regimen of 500 mg b.i.d. may be ineffective in the treatment of soft-tissue infections caused by pathogens with a drug MIC higher than 0.125 mg/liter.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Friederike
authors.initials: F
authors.lastname: Traunmüller
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Petra
authors.initials: P
authors.lastname: Zeleny
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin