Effect of protein binding on penetration of beta-lactams into rabbit peripheral lymph.

Antimicrobial Agents and Chemotherapy
G WoodnuttL Mizen

Abstract

The relevance of protein binding to penetration of beta-lactams into body fluids was investigated by examining the distribution of amoxicillin, ceftriaxone, clavulanic acid, temocillin, and ticarcillin into rabbit peripheral lymph after intravenous administration. The elimination half-lives in rabbit plasma varied between 0.34 h (temocillin) and 1.80 h (ceftriaxone), and the half-lives measured in lymph were similar to those in plasma (0.37 to 1.76 h). The percent penetration (area under the concentration-time curve in lymph/area under the concentration-time curve in plasma x 100) was high for amoxicillin (97.6%), temocillin (89.4%), and clavulanic acid (90.8%) but was lower for ticarcillin (76.0%) and for ceftriaxone (67.3%). There was a direct correlation between plasma protein binding and percent penetration. Correction for plasma and tissue binding increased the percent penetration for all compounds, and figures approached 100%. The results presented demonstrate the use of this model to examine the relationships between plasma pharmacokinetics, protein binding, and distribution of antibiotics.

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Citations

Mar 5, 2002·Journal of Veterinary Pharmacology and Therapeutics·M RebueltoR Hallu
Mar 26, 2003·Antimicrobial Agents and Chemotherapy·William R HumphreyIvan M Richards
May 21, 2010·Journal of Inflammation·Maria SaroglouDemosthenes Bouros
Apr 5, 2013·Clinical Microbiology Reviews·Daniel GonzalezHartmut Derendorf
Jun 12, 2019·Journal of Veterinary Pharmacology and Therapeutics·Benjamin KimbleMerran Govendir
Dec 10, 2020·CPT: Pharmacometrics & Systems Pharmacology·Patrick O HanafinGauri G Rao

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