EFFECT OF PROTEIN-BINDING ON PENETRATION OF BETA-LACTAMS INTO RABBIT PERIPHERAL LYMPH

The relevance of protein binding to penetration of beta-lactams into b ody fluids was investigated by examining the distribution of amoxicill in, ceftriaxone, clavulanic acid, temocillin, and ticarcillin into rab bit 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 und er the concentration-time curve in lymph/area under the concentration- time curve in plasma x 100) was high for amoxicillin (97.6%), temocill in (89.3%), and clavulanic acid (90.8%) but was lower for ticarcillin (76.0%) and for ceftriaxone (67.3%). There was a direct correlation be tween plasma protein binding and percent penetration Correction for pl asma and tissue binding increased the percent penetration for all comp ounds, and figures approached 100%. The results presented demonstrate the use of this model to examine the relationships between plasma phar macokinetics, protein binding, and distribution of antibiotics.