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[ This Week’s Citation Classic SEPTEMBER 1985 Kunin C M. A guide to use of antibiotics in patients with renal disease: a table of recommended doses and factors governing serum levels. Ann. Intern. Med. 67:151-8, 1967. IDepts. Preventive Medicine and Medicine. Univ. Virginia Sch. Med., Charlottesville, VAI This paper provides a table that describes the fachealthy volunteers. I gave an intravenous tors that determine persistence of antibiotics in bolus of each drug to the subjects and drew the serum of patients with renal disease It is blood specimens at periodic intervals therebased on concepts developed by the author and a after. Anthony Glazko of Parke-Davis perreview of the literature. It explains how to adjust formed the chemical assays for chloramthe dosage in order to provide effective therapy phenicol and explained to me the complel with minimal toxicity. [The SCIe indicates that this biotransformation of this drug. paper has been cited in over 200 publications A great deal of data were generated, but! since 1967.] had great difficulty in finding a way to express the information. Christopher Martin, my co-fellow, solved the problem by explaining to me the concept of “half-life in serum,” which he had used in studying the per~ sistence of immunoglobulins in patients Calvin M. Kunin with hypogammaglobulinemia. Sidney lngDepartment of Medicine bar taught me the principles of pharmacoki~ Ohio State University School of Medicine netics, which he was using to study thyroid Columbus, OH 43210-1240 function, and Rudi Schmid helped me inter~ pret data on chloramphenicol, which is con~ jugated in the liver very much like bilirubin~ August 12, 1985 The theoretical concept of this work was based on the mechanisms of clearance of mannitol by 1 the kidney developed by The fundamental work in this field was be- Newman et a!. The advantage of working at gun in 1957, 10 years before the publication the Thorndike lab was that there was a fami~ of this review. I was a fellow in infectious iy atmosphere in which people with divers~ diseases under Maxwell Finland at the interests shared their ideas freely. The unify4 Thorndike Memorial Laboratory, which at ing principles of biology and medicine did that time was part of the Harvard Unit at the the rest. 24 Boston City Hospital. The work was done to The first three papers were submifted tO answer a difficult clinical question raised by the Journal of Clinical investigation and re William Bush, a resident in medicine. He jected. Finland, however, was aroused and had a patient who required streptomycin for asked for another review. The papers were treatment of tuberculosis but had renal fail. finally accepted. The editor evidently feared ure as well. Bush knew that streptomycin Finland’s wrath more than he doubted my, was excreted almost entirely by the kidneys ability. and reasoned that the dose should be adjustI am somewhat surprised that this review ed to prevent toxicity. He expected that paper has been cited more frequently than since I was the infectious disease fellow, I the initial reports. I suppose that the Annals should have the answer. I recommended of internal Medicine has a wide readership. that he reduce the dose. He replied, “How The field has expanded greatly and has been: much?” I didn’t know. I felt guilty and em- extended to virtually all drugs. The FDA re. barrassed by my ignorance and decided to quires pharmacokinetic studies of new~ try to search for an answer. drugs. One can now find recommendations At that time, there were many people with for adjustment of dosage in renal and hepat-j renal failure at the Peter Bent Brigham Hos- ic disease in the drug package inserts. pital, Boston, in John Merrill’s unit. With his An overview of the use of antibiotics as an: permission, I began to study all of the avail- anti-infective agent is formalized in the~ 5 able antibiotics in these patients and in work of Mandell, Douglas, and Bennett. 1. Newman E V. Bordley J, Ill & Winee,nhz iThe interrelationships of glomerular filtration rate mannitol clearance), extracellular fluid volume, surface area of the body. and plasma concentration of mannilol. A definition of extracellular fluid clearance determined by following plasma concentration alter a single injection of mannitol. 11 Bull. Johns Hopkins osp. 75:253-68. 1944. Cited 85 times since 1955.) 2. Kunln C M, Ree. S B, Merrilil P & Finland M. Persistence of antibiotics in blood of patients with acute renal failure. I. Tetracycline and chlortetracycline. I. Cfin. invest. 38:1487-97, 1959. (Cited 125 times.) 3. Kunln C M, Glazko A I & Finland M. Persistence of antibiotics in blood of patients with acute renal failure. II. Chloramphenicol and its metabolic products in the blood of patients with severe renal disease or hepatic cirrhosis.). Clin. invest. 38:1498-508, 1959. Cited 185 times.) 4. Kunln C M & Finland M. Persistence of antibiotics in blood of patients with acute renal failure. III. Penicillin. streptomycin. erythromycin and kanamvcin. .1. Cfin. invest. 38:t509-19. 1959. (Cited 140 times.) 5. Ma.deU G L. Douglas R G. Jr. & Bennetil K. Anti-infectsse therapy. New York: Wiley. 1985. 516 p. 20 ©1985 by ISI® CURRENT CONTENTS®