Does serum protein binding inhibit tissue penetration of antibiotics?

Accumulated data on the penetration of 15 antibacterial agents into peripheral human lymph are reviewed. The major factor determining extravascular penetration is the level of serum protein binding. The penetration ratios of extravascular and serum levels diminish gradually as the level of protein binding increases. However, even at the highest protein-binding levels, distinct lymph concentrations are observed. The degree of penetration ranges from 100% for the antibiotic with the lowest level of serum protein binding (gentamicin, no drug bound) to 20% for that with the highest level of protein binding (flucloxacillin, 96% bound).