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Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers
Author(s) -
Hollenstein Ursula,
Brunner Martin,
Mayer Bernhard X.,
Delacher Simon,
Erovic Boban,
Eichler Hans Georg,
Müller Markus
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.104266
Subject(s) - bolus (digestion) , cefpirome , trough concentration , antibiotics , dosing , medicine , microdialysis , pharmacokinetics , minimum inhibitory concentration , subcutaneous tissue , antibacterial agent , anesthesia , pharmacology , chemistry , surgery , central nervous system , biochemistry , antibiotic resistance , imipenem
Background Recent data indicate a higher level of effectivity of β‐lactam antibiotics if serum concentrations are kept above the minimal inhibitory concentration (MIC) of the pathogen. This concept would favor continuous infusion over bolus dosing. However, it is usually not the serum concentration but the free interstitial concentration in the target tissue that determines antibiotic activity. We therefore set out to measure effective drug concentrations in the interstitial space of muscle and subcutaneous adipose tissue and to compare trough levels and times above the MIC after bolus versus continuous infusion of cefpirome. Methods Twelve healthy volunteers received a single dose of 2 g cefpirome as an intravenous bolus or as a continuous infusion over 8 hours in a crossover design, and the resulting free interstitial tissue concentrations were measured with use of microdialysis. Results After bolus injection, mean interstitial trough concentrations were 3.0 ± 1.9 μg/mL and 2.1 ± 1.0 μg/mL for muscle and subcutaneous tissue, respectively; continuous infusion resulted in trough levels of 10.1 ± 6.8 μg/mL and 10.1 ± 4.6 μg/mL for muscle and subcutaneous tissue, respectively. This resulted in significantly longer times above the MIC with continuous infusion for Staphylococcus epidermidis and Enterobacter cloacae . Bacteria with an MIC ≤1 would be covered by either method, whereas higher doses seem to be necessary for Pseudomonas aeruginosa . Conclusion Although susceptible organisms will usually be covered sufficiently with standard dosing regimens, soft tissue infections with bacteria that have MIC values of 2 to 8 may profit from continuous application. Coverage of P aeruginosa , however, would be inadequate with conventional daily doses of 4 g cefpirome regardless of the method of application. (Clin Pharmacol Ther 2000;67:229–36.) Clinical Pharmacology & Therapeutics (2000) 67 , 229–236; doi: 10.1067/mcp.2000.104266