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