G concentrations of rabbits given intramuscular injections of aqueous crystalline penicillin G. Probenecid increased CSF penicillin concentration because the drug was removed more slowly by the inhibited organic acid pumping mechanism in the choroid plexus. Note that at this dose there was also a detectable early increase in serum pericillin concentration. This means of increasing CSF penicillin concentration has been used experimentally in the treatment of CNS infections caused by resistant Neiserria gonorrhea . Effect of probenecid on serum and CSF penicillin G concentrations. Open symbols are controls.
Closed symbols are in the presence of probenecid.
Squares represent CSF and circles represent serum penicillin G concentration. Protein binding is low to moderate for all penicillin derivatives except the isoxazolyl derivatives, e.g., cloxacillin and dicloxacillin. The primary concern with such high binding is the potential it provides for interacting with other drugs that are also highly protein bound. Some reach therapeutic concentrations in bile, for example, ampicillin, but are ultimately eliminated in the urine. Biotransformation is not a significant factor with these drugs.