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Serum and subcutaneous chamber fluid (CF) dynamics of penicillin G, ampicillin, and amoxicillin were studied in rabbits after single large parenteral doses comparable to doses used in treating gonorrhea and endocarditis. The effects of parenteral probenecid and of injection of an antibiotic directly into a subcutaneous chamber ("intrachamber" injection) also were studied. Peak serum antibiotic concentrations exceeded peak CF concentrations and occurred sooner. Antimicrobial activity persisted longer in CF than in serum. Percent penetration [100 x (CF peak/serum peak)] of CF was least after intramuscular ampicillin and amoxicillin, was greatest after intrachamber ampicillin and intramuscular aqueous procaine penicillin G, and was related to duration of antibiotic concentration gradients from serum to CF. Intramuscular aqueous crystalline penicillin G resulted in higher serum and CF penicillin G concentrations than intramuscular aqueous procaine penicillin G, which prolonged the duration of penicillin G in serum and CF. Amoxicillin diffused into CF more readily than ampicillin. Probenecid resulted in higher early serum and CF antibiotic concentrations, but had little or no effect on duration of antibiotic activity. Intrachamber ampicillin resulted in more prolonged serum and CF ampicillin activity than intramuscular ampicillin, but much lower peak serum concentrations. The data suggest a possible means by which probenecid improves the efficacy of gonorrhea therapy with aqueous procaine penicillin G. Intrachamber administration of penicillins could be useful in treating experimental infections requiring prolonged therapy.

Serum and Subcutaneous Chamber Fluid Dynamics of Penicillins After Single Large Parenteral Doses