Quantitative binding of penicillin G to tissue homogenates as determined with the preparative ultracentrifuge.

The preparative ultracentrifuge was used to determine quantitative binding of penicillin G to rabbit serum and homogenates of muscle, liver, kidney, bone, lung, spleen, brain, skin, heart, and pancreas. At 10 U/ml rabbit serum bound 46.7% of penicillin G, and all tissues bound 9.0% or less. The ultracentrifuge method was reliable and reproducible and eliminated problems encountered in other methods used to study antibiotic-tissue binding. The results demonstrate only minor extravascular binding of penicillin G and allow prediction of total achievable tissue levels from knowledge of the concentration of unbound drug in the serum at equilibrium and the fraction of drug bound to each tissue. The small amount of extravascular penicillin G- tissue binding found would be expected to lower predicted serum levels by only 3.1%.