THE VARYING BLOOD LEVELS AFFORDED BY PENICILLINS F, G, K, AND X IN RABBITS AND MAN

1. In both man and rabbit, penicillin X provided higher and more sustained blood levels than did penicillins F or G similarly administered in equal dosage (0.6 mg. per kg.); while penicillin K gave lower and evanescent levels. (a) One hour after intramuscular injection, the blood levels in rabbits averaged 0.11, 0.18, 0.02, and 0.33 for F, G, K, and X, respectively; and levels of 0.1 mg. per kg. were sustained for 1, 1.4,0.5, and 2.1 hours, respectively. (b) In man, the blood levels of G, K, and X averaged 0.23, 0.16, and 0.37 mg. per kg. 1 hour after intramuscular injections at 0.6 mg. per kg., and 0.11, 0.02, and 0.15 mg. per kg. 1 hour after intravenous injection. (c) In man, a level of 0.1 microgram per cc. was sustained for 1.6, 1.2, and 2.3 hours after the intramuscular injection of G, K, and X, respectively, and for 1, 0.5, and 1.3 hours after their intravenous injection. 2. The total urinary recovery of penicillins F, G, and X varied between 68 and 100 per cent, averaging 61, 87, and 74 per cent, respectively, in rabbits. In man, the urinary recovery of G and X averaged 86 and 93 per cent, respectively. In sharp contrast, the urinary recovery of penicillin K averaged 33 per cent in seven rabbits and 28 per cent in six human volunteers. The major portion of the penicillin appeared in the first 30 to 60 minutes. This suggests a rapid inactivation of penicillin K in vivo. 3. The therapeutic significance of these data is discussed in the text, and in greater detail in the following paper.