title: Effect of protein binding on penetration of beta-lactams into rabbit peripheral lymph.
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.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, England.
authors.forename: G
authors.initials: G
authors.lastname: Woodnutt
authors.forename: V
authors.initials: V
authors.lastname: Berry
authors.forename: L
authors.initials: L
authors.lastname: Mizen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D006207:Half-Life; D008196:Lymph / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D014018:Tissue Distribution; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams