G. Woodnutt et al., EFFECT OF PROTEIN-BINDING ON PENETRATION OF BETA-LACTAMS INTO RABBIT PERIPHERAL LYMPH, Antimicrobial agents and chemotherapy, 39(12), 1995, pp. 2678-2683
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.