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November 20, 1948

CARONAMIDE AND PENICILLIN: Serum Levels in Human Beings, Following Multiple Doses of the Drugs

Author Affiliations

Winston-Salem, N. C.

From the Department of Internal Medicine, Bowman Gray School of Medicine of Wake Forest College and the North Carolina Baptist Hospital, Winston-Salem.

JAMA. 1948;138(12):874-877. doi:10.1001/jama.1948.02900120016004

Numerous attempts have been made to increase the efficacy of penicillin in the treatment of infections by altering the rate of its absorption or excretion. Beyer and his associates have reported that caronamide (4′-carboxyphenylmethanesulfonanilide), though excreted only by the glomeruli, alters the specific renal tubular enzyme system responsible for the excretion of penicillin.1 The excretion of penicillin is delayed, so that a higher concentration may be maintained in the blood for more prolonged periods. Other investigators have confirmed the original reports on the penicillin-enhancing effect of caronamide and have noted that the drug is relatively nontoxic when administered over short periods of time.2

There is difference of opinion concerning the dose of caronamide necessary to maintain an effective concentration of penicillin in the blood. Direct information on the absorption and excretion of caronamide in human beings has been lacking, since practical methods of measuring the concentrations of the

Beyer, K. H.:  New Concept of Competitive Inhibition of the Renal Tubular Excretion of Penicillin ,  Science 105: 94-95 ( (Jan. 24) ) 1947.Crossref
Beyer, K. H.; Miller, A. K.; Russo, H. F.; Patch, E. A., and Verwey, W. F.:  The Inhibitory Effect of Caronamide on the Renal Elimination of Penicillin ,  Am. J. Physiol. 149: 355-368 ( (May) ) 1947.
Beyer, K. H.; Russo, H. F.; Patch, E. A.; Tillson, E. K., and Shaner, G.:  Certain Pharmacologic Properties of 4′-Carboxyphenylmethanesulfonanilide (Caronamide), Including Its Effect on the Renal Clearance of Compounds Other Than Penicillin ,  J. Pharmacol. & Exper. Therap. 91: 272-287 ( (Nov.) ) 1947.
Seeler, A. O.; Wilcox, C., and Finland, M.:  Enhancement of Blood Levels by Caronamide During Intramuscular Administration of Penicillin ,  J. Lab. & Clin. Med. 32: 807-817 ( (July) ) 1947.
Strauss, E.; Richburg, P. L.; Saba, P. Z., and Alexander, J. E.:  Enhancement of Plasma Penicillin Concentrations by Caronamide and Sodium Benzoate ,  J. Lab. & Clin. Med. 32: 818-831 ( (July) ) 1947.
Crosson, J. W.; Boger, W. P.; Shaw, C. C., and Miller, A. K.:  Caronamide for Increasing Penicillin Plasma Concentrations in Man ,  J. A. M. A. 134: 1528-1532 ( (Aug. 30) ) 1947.
Shaw, C. C.; Boger, W. P.; Crossen, J. W.; Kemp W. W.; Ling, W. S. M., and Duncan, G. G.:  Enhancement of Penicillin Blood Levels in Man by Means of a New Compound, Caronamide ,  Am. J. Med. 3: 206-210 ( (Aug.) ) 1947.
The penicillin used in this study was supplied by Wyeth, Inc., Philadelphia.
Sharpe and Dohme, Inc., Philadelphia, furnished the caronamide used in this study. Dr. William P. Boger, associate medical director, made available to us the results of several of his studies prior to their publication.
Ziegler, C., and Sprague, J. M.:  A Colorimetric Determination of Caronamide ,  J. Lab. & Clin. Med. 33: 96-100 ( (Jan.) ) 1948.
Boger, W. P.; Kay, C. F.; Eisman, S. H., and Yoeman, E. E.:  Caronamide, a Compound That Inhibits Penicillin Excretion by the Renal Tubules, Applied to the Treatment of Subacute Bacterial Endocarditis ,  Am. J. M. Sc. 214: 493-502 ( (Nov.) ) 1947.
Beyer, K. H.; McKinney, S. E.; Tillson, E. K., and Green, C. W.:  4′Carboxyphenylmethanesulfonanilide (Caronamide): Its Toxicologic Effects ,  J. Pharmacol. & Exper. Therap. 91: 263-271 ( (Nov.) ) 1947.
Earle, D. P., Jr., and Brodie, B. B.:  The Renal Excretion of 4′-Carboxyphenylmethanesulfonanilide (Caronamide) ,  J. Pharmacol. & Exper. Therap. 91: 250-254 ( (Nov.) ) 1947.