ABSORPTION, DISTRIBUTION, AND EXCRETION OF IMIDOCARB DIPROPIONATE (3,3'-bis-(2-imidazolin-2-yl) carbanilide) IN SHEEP
ABSORPTION, DISTRIBUTION, AND EXCRETION OF IMIDOCARB DIPROPIONATE (3,3'-bis-(2-imidazolin-2-yl) carbanilide) IN SHEEP
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Date
1974-08
Authors
YUSUF, OTARU ALIU
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Abstract
ABSORPTION, DISTRIBUTION, AND EXCRETION OF
IMIDOCARB DIPROPIONATE
(3,3'-bis-(2-imidazolin-2-yl) carbanilide)
IN SHEEP. (August 1974)
Yusuf Otaru Aliu, D.V.M., Cornell University.
Spectrophotometric and thin-layer chromatographic
methods for quantitative and qualitative determination
of imidocarb in biologic specimens are described.
Imidocarb was extracted under basic conditions from
plasma, urine, milk, bile and homogenized tissue samples
into organic solvents. Following extraction and concentration
in 0.82 N HCl, the drug can be qualitatively
identified by thin-layer chromatography and spectrophotometry.
The detection limit for estimation of pure
imidocarb in aqueous solution by spectrophotometry is
equivalent to a concentration of 1.0 μg/ml in plasma
and other body fluids and 5.0 μg/Gm in tissues. With
thin-layer chromatography, the minimum detection level
is 0.21 μg.
Following intravenous injection of imidocarb
dipropionate (2.0 mg/kg of body weight) into sheep, the
high initial plasma concentration of 10.8 μg/ml fell
very rapidly to 1.9 μg/ml in 1 hour, and was less than
1 μg/ml in 4 hours post injection. When 4.5 mg/kg of
body weight of imidocarb was injected intramuscularly
into sheep, peak plasma concentrations of 7.9 μg/ml
were attained within 4 hours. This was followed by a
rapid decline within the next 2 hours to 4.6 μg/ml, and
then by a very slow decline of several weeks duration.
Trace amounts were still present in the plasma 4 weeks
after treatment. The drug was bound to plasma proteins
to the extent of 21-53%, and the apparent volume of
distribution was slightly higher than the total body
water.
Imidocarb was widely distributed in the tissues of
sheep. Concentrations in the tissues studied were considered
high and detectable amounts were present 4 weeks
after administration. Twenty-four hours after administration,
the highest concentrations occurred in the
kidneys, liver and brain. Using 14C-labelled imidocarb
to study its distribution in the brain, significant
radioactivity was detected in all regions with highest
concentrations occurring in the pituitary gland, the
pineal body and the olfactory bulb. The concentrations
of radioactivity measured in plasma (0.013 μg/ml) and
sheep red blood cells (0.016 μg/ml) indicated an equal
partitioning between plasma and red blood cells.
No metabolic or biotransformation products could
be detected by the methods of assay. Approximately
11-17% of the administered dose was excreted in the
urine within 24 hours; thereafter, the excretion rate
was very low and detectable amounts were present for 4
weeks. The rate of renal clearance of imidocarb was
found to be considerably below glomerular filtration
rate indicative of tubular reabsorption.
The relatively high concentrations of the drug
found in the bile suggest that biliary excretion of
imidocarb is an important route of excretion. High
concentrations were also found in the milk of lactating
ewes. When the milk was fed to nursing lambs, no drug
could be detected in their plasma.
Imidocarb did not affect oxidative phosphorylation
of isolated rat liver mitochondria.
Description
A Dissertation Submitted to the Graduate College of
Texas A&M University in
partial fulfillment of the requirement for the degree of
DOCTOR OF PHILOSOPHY
August 1974
Keywords
ABSORPTION,, DISTRIBUTION,,, EXCRETION,, IMIDOCARB,, DIPROPIONATE,, carbanilide,, SHEEP