THE RENAL CLEARANCE OF PENICILLINS F, G, K, AND X IN RABBITS AND MAN 1

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Abstract
The renal clearance of penicillins F, G, and X in man was found to approximate the total renal plasma flow and was approx. 4-5 times the renal clearance of inulin or Na thiosulfate. The penicillin clearance was independent of the absolute blood level over the entire range 0.05-10 -[gamma]/ml. and independent of the rate of urine flow. Penicillin may be used in lieu of para-aminohippuric acid or diodrast as a test of renal plasma flow and renal function. The renal clearance of penicillin K in man was 1/4-1/2 that of F, G, or X. Two possible explanations for this anomalous result are discussed. The tubular excretory mechanism was completely saturated in 2 rabbits receiving 600 mg./kg. of peni-cillin G. In these, the initial blood levels were 2,667 and 3,200 7 and the initial renal clearances of 3 and 7 ml,/minute corresponded to the glomerular filtration rate. As the serum conc. fell to less than the saturation level for the tubular mechanism, the renal clearances rose to normal levels of 18-28 and 23-57 ml./minute. Although no differences were found between the renal clearance of penicillins F, G, or X, it is suggested that penicillin derivatives may be produced with significantly lower clearances than those of the natural penicillins so far identified and with correspondingly enhanced therapeutic activity in vivo.