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+Calibration
Date
CLINICAL PHARMACOLOGY
The
renal clearance of sodium iothalamate in man closely approximates that
of inulin. The cmpd is cleared by glomerular flitration w/out tobular
secretion or reabsorption. Following infusion administration of I-125
iothalamate, the effective half-life is about 0.07 days.
INDICATIONS AND USAGE
GLOFIL-125 (Sodium Iothalamate I-125 Injection) is indicated for
evaluation of glomerular filtration in the diagnosis or monitoring of
patients with renal disease.
CONTRAINDICATIONS
None known.
WARNINGS
None known.
PRECAUTIONS
General
As in the use of any radioactive material, care should be taken to
minimize radiation exposure to the patient, consistent with proper
patient management, and to insure minimum radiation exposure to
occupational workers.Radiopharmaceuticals should be used only by
physicians who are qualified by trainiing and experience in the safe use
and handling of radionuclides.Rapid or bolus-like injections should be
avoided.
Carcinogenesis, Mutagenisis, Impairment of Fertility
No long-term animal studies have been performed to evaluate
carcinogenic potential, mutagenic potential, or whether this drug
affects fertility in males or females.
Pregnancy Category C
Animal reproduction studies have not been conducted with GLOFIL-125.
It is also not known whether GLOFIL-125 can cause fetal harm when
administered to a pregnant woman or can affect reproduction capacity.
GLOFIL-125 should be given to a pregnant woman only if clearly needed.
Nursing Mothers
Radioiodine is excreted in human milk during lactation. It is not
knoen whether GLOFIL-125 is excreted in himan milk. Therefore, formula
feedings should be substituted for breast feedings.
Pediatric Use
Safety and effectiveness in children have not been established.
ADVERSE REACTIONS
None reported.
DOSAGE AND ADMINISTRATION
Dosage
The suggested dose range employed in the average patient (70 kg) is
as follows:Continuous intravenous infusion: 20 to 100 uCi (0.74-3.7
megabecquerels) (Sigman, et al.1 method).Single intravenous
injection: 10 to 30 uCi (0.37-1.11 megabecquerels) (Cohen, et al.2
method).The patient dose should be measured by a suitable radioactivity
calibration system immediately prior to administration.
TechniqueContinuous intravenous infusion
1. Preparation:
A. Adequae diuresis (a urine flow exceeding 3 mL/min.) is
established, preferably by an oral water load of 1,500 mL two hours
prior to the beginninh of the clearance study.
B. It is not necessary to withhold breakfast or admit the patient
the night before.
2. Procedure:
A. After the establishment of adequate diuresis, a number 14 or 16
French Foley catheter is aseptically inserted into the bladder.
B. An intravenous infusion of Lactated Ringer's (Hartmann's)
solution is started in each arm, one to maintain a site for injection of
the GLOFIL, the other to serve as a site for serial withdrawal of blood.
A two-way stopcock connects the needle and intravenous tubing of each
arm.
C. The dose is equally divided into (1) an intravenous priming
dose to be injected as is and (2) a sustaining dose to be diluted in 30
to 60 mL of isotonic sodium chloride, depending on how many collection
periods are anticipated.
D. The priming dose is sloewly injected into one arm. This is
immediately followed by infusion of the sustaining solution through the
same site, usually at the rate of 0.5 mL/min., by means of an automatic
pump. During this infusion, the Lactated Ringer's solution in the
same same arm is discontinued, and 40 to 45 minutes are allowed for
equilibration in order to reach a state of constant plasma concentration
of radioactivity.
E. After attaining equilibration, consecutive 15 minute
collection periods are started. From the arm opposite the injection
site, 5 mL of blood (allowing duplicate plasma counting volumes) is
drawn six minutes prior to the midpnt of each collection period, placed
in heparinized tubes, mixed, and centrifuged. The blood sampkes may be
obtained through the two-way stopcock after discarding the first 30 mL
aspirated into the syringe. This 30 mL contains the contents of the
tubing, including infusion fluid, and must be cleared in order to obtain
an undiluted blood sample. If desired, this step may be eliminated and
blood samples obtained by direct venipuncture.F. During each
collection period, total urine must be accurately collected and the
volume accurately measured. Three such consecutive collection periods
are sufficient for most clinical studies.
3. Clearance Calculations:
A. Aliquots (1 mL each) of plasma and urine from each collection
period are counted in a standard gamma-ray scintillation well director.
B. All counts are corrected for background activity.
C. Glomerular filtration rate is calculated by the formula
C=UV/P, in which:
C= glomerular filtration rate in mL/min
U= urinary concentration of radioactivity in net counts/min/mL
V= urinary flow rate in mL/min
P= plasma concentration of radioactivity in net counts/min/mL
D. Average glomerular filtraytion rate (GFR) is calculated from
the rates for the individual collection periods. GFR can be expressed in
terms of body weight (mL/min/kg) or body surface area (mL/min/m2).
E. Unilateral glomerular filtration rates can be deternined by
the same techniqyue by utilizing ureteral catherization.
Single intravenous injection
Cohen's Method:
The method of Cohen, et al.2 requires little preparation,
few and small blood samples, no bladder catherization, and no constant
intravenous infusion. It is simple to perform, rapid, and utilizes
equipment which is readily available in most modern laboratories.
1. Preparation:
A. Lugol's solution, 3 drops orally, three times a day, is
administered for one or two days prior to the test.No diet or water
restriction is necessary.
B. Oral water load is begun one hour before starting the test.
Start with 20 mL/kg and force any clear liquids (unless contraindicated)
until the test is complete.
2. Procedure:
Record actual times for teh collection of the blood and urine samples.
A. Empty the bladder and label the urine Urine control.
B. Inject 10-30 uCi GLOFIL-125 intravenously; wait 30 to 60
minutes.
C. Collect the entire urine and label Urine discard.
D. Draw 4 to 5 mL of blood into a heparinized syringe. Label
Plasma #1 .
E. After another 30 to 60 minutes, collect the entire urine and
label Urine #1.
F. Immediately draw another blood specimen. Label Plasma
#2.
G. After final 30 to 60 minute wait, collect the urine. Label
Urine #2.
H. Draw the last blood specimen immediately. Label Plasma #3.
3. Clearance Calculations:
1. Radioactivity of one mL aliquots of both urine and plasma are
determined using a well-scintillation detector with a single channel
pulse-height analyzer. Sufficiently reproducible counts are usually
obtained with time settings of 2 minutes for urine samples and 20
minutes for the plasnma samples. Calculations of the clearance rates are
made by using the formula:
C=(UV/P) + (1.73/SA) where:
C= glomerular filtration rate in mL/min
U= urine radioactivity in counts/min/mL
V= urine flow rate in mL/minP= mean plasma radioactivity in
counts/min/mL
SA= body surface area in m2
Radiation Dosimetry
The estimated absorbed radiation doses to an average (70 kg) patient
from an intravenous dose of 100 uCi (3.7 megabecquerels) of GLOFIL-125
are shown in Table 4. Calculations assume that there is 1% feree iodide
in the preparation and that the thyroid uptake of the iodine is 25%.
Table 4
Absorbed Radiation Doses***
Absorbed radiation doses for 100 uCi (3.7 megabecquerels) |
