INFECTIOUS
Circadian Linda
Elting,
DISEASES
Variation in Serum Amikacin Levels
DrPH,
Gerald and
P. Bodey, Victor
MD,
F’ainstein,
Beverly
Rosen
baum,
BA,
MD
Variable serum amikacin levels have been reported in the same patient even after a steady state presumably has been reached. Therefore, the authors investigated the optimal schedule for monitoring serum levels of the drug in 50 neutropenic patients receiving continuous infusion amikacin therapy for infections. We found that levels obtained in the early morning hours were significantly higher than those obtained for the same patient in the evening. As these differences parallel those previously demonstrated for renal function, they may be explained by the pattern of drug clearance by the kidneys. We recommend that blood specimens for the detection of rising serum amikacin levels in a therapeutic setting be obtained in the early morning and at the same time each day so that meaningful comparisons of peak concentrations can be made. However, late evening samples should also be tested whenever dosage modifications are considered so that continuous therapeutic serum concentrations can be ensured.
I
n the neutropenic glycosides by
patient, continuous
administering intravenous
aminoinfusion
may be more effective than using conventional intermittent infusion methods.1’2 Although infusion pumps deliver a constant dose of aminoglycoside, serum ably
in
levels the
presumably
have same
had
been patient,
been
observed even
reached.3
to vary considerafter a steady state
For
this
reason,
the
possible influence of time of day on amikacin serum level was investigated. Since renal function is known to vary predictably with time of day, and since amikacin is excreted by the kidneys, we hypothesized that the differences observed anecdotally could be due to the time of day that levels were
drawn. Three samples were obtained in each patient; at 7:00 AM, 3:00 PM, and 9:00 PM. One of these samples was obtained on each of three days (days 3, 5, and 7) after a steady state presumably had been reached. The day on which each timed sample was obtained was randomly assigned in order to avoid bias due to duration of therapy. All patients received amikacin 800 mg/M2/day. Patients with abnormal renal function or creatinine clearance were excluded. Serum levels were determined by fluorescent polarization using the Abbott TDX (Abbott Laboratories, North Chicago, IL). Data were analyzed using paired t tests, in which each patient served as his own control, as well as with unpaired t tests.
measured. MATERIALS As a part
with with
AND of a clinical
METHODS study
continuous infusion either ceftazidime
patients at which
were randomly their serum
RESULTS of therapy
amikacin or imipenem, assigned amikacin
of infections
in combination neutropenic
to the levels
time of day would be
From the Section of Infectious Diseases, Department of Medical Specialties, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Address for reprints: Linda Elting, DrPH, Infectious Diseases/(Box 47), M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030.
798
#{149} J ClIn Pharmacol
1990;30:798-801
Fifty consecutive patients who had been previously randomized to receive either amikacin plus ceftazidime or amikacin plus imipenem were included in this study. Three patients were considered inevaluable because they either developed renal dysfunction during the study (1 patient) or were changed to other antibiotics before the study was completed (2 patients). Demographic characteristics of the 50 patients were equally distributed; 23 were men, 24 received ceftazidime and their median age was 45 years.
CIRCADIAN
Patients confounding received sampling.
did
not factors
VARIATION
differ significantly measured. None
IN
function
diuretics None
and, although freely. All of the as
measured
hospitalized, patients had
by
serum
all were amnormal renal
creatinine