119
El sayed et al
. /
International
Journal of Biopharmaceutics.
201
5
;
6
(
3
):
115
-
120
.
DISCUSSION
In this study
,
the
obtained results
indicated that
cefotaxime could be detected in a therapeutic level for 8
hours in plasma following repeated
intramuscular
administrations. These
c
oncentrations (1.73 μg/ml)
exceeded the minimum inhibitory concentration (MIC)
for sensitive
Salmonella
typhimurium
to cefotaxime. The
minimum inhibitory concentration (MIC
90
) of cefotaxime
was (0.016
-
1 μg/ml)
(Knudsen
et al.,
1997)
which most
effective ag
ainst the majority of sensitive Gram
-
positive
and Gram
-
negative pathogens.
A
n average MIC
90
of 1.73 μg/mL of cefotaxime
has been considered. Based on this data, the
intramuscular injection of cefotaxime at a dose of 50
mg/kg at 8 h interval is suf
ficient to maintain plasma
concentration above MIC
90
for most sensitive susceptible
pathogens (g/m); these findings indicate the suitability of
successful use of cefotaxime in goats. A recommended
three daily dose of 50 mg/kg of cefotaxime given
intramuscu
larly achieves therapeutic concentrations in
plasma exceeding the MIC
90
against different susceptible
pathogens in goats.
The relative higher plasma concentrations of
cefotaxime after the last dose compared to the first doses
indicated the accumulati
on of cefotaxime in blood during
multiple dosing at 8 hours intervals for five consecutive
days. These observations agreed with data reported
by
El
-
Hewaity
et al.,
(
2014).
The obtained result was inconsistent with that
reported by
Ing
e
s
et al.,
(
19
82)
When cefotaxime was
administered repetitively in patients, the ratio of maximal
serum levels after the last dose to those after the first
dose demonstrated minimal accumulation of intact drug
and
by
Sharma and Srivastava
et al.,
(
2003)
who found
that
a lack of cumulative effect after repeated
intramuscular injection of cefotaxime in buffalo calves.
The study showed that the blood concentrations
of cefotaxime in
Salmonella
typhimurium
infected goats
were significally lower than those in normal
goats
following repeated intramuscular injection.
These lower
blood concentrations in
Salmonella
typhimurium
infected
goats might be attributed to the higher penetrating power
of cefotaxime to the diseased tissues
(Baggot, 1980)
.
This
phenomenon was simil
ar to data recorded by
Abdulgafar
et al.,
(
2011)
and
El
-
Sayed
et al.,
(1994)
The maximum [C
max
] and minimum plasma
concentration of cefotaxime during multiple regimen in
normal
(12.03,
1.73
μg/ml)
respectively
and
experimentally
Salmonella
typhi
murium
infected goats
(4.06, 0.623 μg/ml) respectively, this indicated that dose
regimen of 50 mg/kg b.wt every 8 hours for five days
would provide effective and safe concentrations exceeded
MIC for most microorganism sensitive to cefotaxime .
The
highest concentrations of cefotaxime in
milk were recorded 4 hours after each
intramuscular
injection with a
significant
lower
value in
Salmonella
typhimurium
infected goats than in normal goats.
This
might be attributed to accumulation of drug in the
infl
ammed tissues
(Baggot, 1980)
. This result is similar
to those reported by
El
-
sayed
et al.,
(1989) and (1994)
who found that
milk
concentrations of gentamicin and
cephradine were significantly lower in infected goats and
cattle than in normal ones, respecti
vely.
Cefotaxime have three ionization groups:
carboxylic, amide and aminothiazole
(Aleksic
et al.,
2005)
, these compounds are sufficientaly libid
-
soluble to
be able to penetrate tissues.
The study showed that, the urine concentrations
of cefota
xime were greater than the concurrent plasma
concentrations following intramuscular injection. This
observation is similar to those reported in cows after
cephapirin administrations
(Prades
et al.,
1988)
.
The high concentrations of cefotaxime in ur
ine
of goats are indicat
or
for renal elimination and are
considered the main route of elimination of the drug.
These results consistent with those reported by
Luthy
et
al.,
(
1979
)
,
Nielsen
et al.,
(
1980
)
,
Inges
et al.,
(
1982
)
,
Ohkawa
et al.,
(
1983
)
and
Ma
tzke
et al.,
(
1985)
reported
that approximately 40 to 60% of cefotaxime was excreted
renally in adults with normal renal function
.
Molinoff
et
al.,
(
1996)
reported that
cephalosporin derivatives are
generally excreted
through
the kidney by glomerular
filt
ration and active tubular secreation.
In the present study, urine concentrations of
cefotaxime increased with the repetition of dosing. This
observation supported
by
Holazo
et al.,
(
1986)
after
repeated intramuscular administrations o
f ceftriaxo
ne in
healthy volunteeres.
CONCLUS
ION
The present study concluded that:
Plasma concentrations of cefotaxime in normal and
Salmonella
typhimurium
infected goats
could be detected
in a therapeutic level for 8 hours in plasma following
repeated
in
tramuscular
administrations.These
concentrations
exceeded the minimum inhibitory
concentration (MIC) of
Salmonella
typhimurium
to
cefotaxime a factor indicating that cefotaxime is adrug of
choice for
Salmonella
typhimurium
infection.
The high concentration
s of cefotaxime in urine,
suggest
ed
that cefotaxime is a suitable antimicrobial for
treatment of urinary tract infections
The high milk concentrations of cefotaxime in
lactating goats suggest
ed
that cefotaxime could be used
for treatment of mastitis
Mossad Gamal El-Sayed 
Ashraf Abd El-Hakim El-Komy 
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