T H E Varying Blood Levels Afforded by Penicillins F, G, K, and X in Rabbits and Man by Harry Eagle, M.d. with the Technical Assistance of Arlyice

I t has been shown in the preceding paper (1) that penicillins F, G, K, and X are all inactivated by serum, plasma, and whole blood, but at widely varying rates. Penicillin X was inactivated slowly (5 to 7 per cent per hour in 96 per cent human or rabbit serum at 37°C.); F and G somewhat more rapidly (8 to 10 per cent per hour); while the rate of inactivation of K varied with its concentration. In human serum, it averaged 10 per cent per hour at a concentration of 50 micrograms per co. (115 units per cc.), increasing to 11, 14, and 50 per cent per hour at concentrations of 10, 2, and 0.4 micrograms per cc., respectively. The corresponding values in rabbit serum were 10, 16, 21, and S0 per cent per hour. The value of 50 per cent per hour at penicillin concentrations of 1:2,500,000 (0.4 microgram per cc.) had no quantitative significance because of the large error in the bioassay of penicillin at such low concentrations in the presence of serum; but the qualitative trend was definite. As will be shown in the present paper, these results in vitro are precisely paralleled by the behavior of the same penicillins in dvo. When F, G, K, and X were injected into rabbits or man in gravimetrically equal amounts per kilo (and thus, approximately equimolar amounts), penicillin X regularly gave higher and more sustained blood levels than either F or G. 1 Penicillin K, on the other hand, regularly gave low and evanescent blood curves, associated with a low recovery in the urine, and suggesting a rapid inactivation in dvo. The correlation between the varying rates of destruction of these penicilllns in serum in dtro, and the correspondingly varying blood levels observed after their injection in dvo, strongly suggests a causal relationship. The possibility that the substances in serum which inactivate penicillin may be present in even higher concentration in some of the body tissues is discussed in the text. Metkods and Materials The peniciUins used in these studies, and the methods of their assay, have been described in the previous paper. In addition to the penicillins there listed, there were used in the present