Renal tubular excretory capacity for penicillin in health and in subacute bacterial endocarditis

Abstract

I T has been amply shown that penicillin is largely excreted by the kidneys without appreciable destruction in the body’ and that this process occurs rapidly’ thus playing an important part in limiting the usefulness of that drug in the treatment of infection. The belief that penicillin leaves the kidneys not only through glomerular filtration but also by tubular excretion has been substantiated by the work of Rantz and Kirby2 on penicillin clearances. These investigators showed that the amount of blood cleared of penicillin by the kidneys per minute compared with that cleared of diodrast, another substance excreted by the renal tubules.3 In addition the clearance values of penicillin are far higher than those of such drugs as inulin which is known to be excreted solely by glomerular filtration. Rammelkamp and Bradley,4 who showed that elimination of penicillin is retarded when penicillin and diodrast are given simultaneously, suggested that there existed between these two drugs a competition for the same mechanism of tubular excretion. This has also been shown to be true of paraaminohippuric acid. 5 It was of practical importance, therefore, to know the maximal tubular excretory capacity (TM,) of the kidneys for penicillin since doses of the drug surpassing TM, would be expected to produce relatively more rapid rises in the blood levels of penicillin than amounts under this level. It is already known that with renal damage penicillin excretion is hindered along with other renal functions and that high and sustained blood levels may follow relatively small doses. 6 In diseases in which renal damage occurs and which are susceptible to treatment with penicillin renal failure might then paradoxically exert a favorable influence on the direct outcome of the illness. One disease to which these events are applicable is subacute bacterial endocaiditis which in most cases has been found highly amenable to penicillin and in which a high percentage of cases has more or less renal damage.’ It is of interest then to know of how much importance the renal damage in subacute bacterial endocarditis is in producing higher than usual blood levels of penicillin. Loewe, Rosenblatt and Alture-Werber8 found that in a case of a patient with resistant endocarditis receiving large doses of penicillin by continuous intravenous drip the serum levels of penicillin began to rise above the expected levels when a dose of 625,000 units per hour was reached. It was suggested that at this. dosage the TM of penicillin had been attained. It has been shown that with lower continuous intravenous dosages the rise in serum penicillin concentration is directly proportional to the increase in dose.2 With these points in mind, serum levels, urinary excretion and serum clearances of penicillin in normal individuals and in patients with subacute bacterial endocarditis have been studied. * From the Department of Medicine, Stanford University School of Medicine, San Francisco, Calif.