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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.
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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~
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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.
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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.
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