الفهرس 
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Abstract
The pharmacokinetics of piroxicam and cimetidine were studied on 20 female lactating goats (12 normal and 8 arthritic) and the goats divided into 5 group each one consist from 4 goats following intravenous and intramuscular injections. Bioavailabilities of both drugs were calculated in normal goats after a single intramuscular dose . The effect of cimetidine on the disposition kinetics of piroxicam , its clearance , urine output and creatinine clearance were investigated in normal and arthritic goats following a single and repeated intramuscular co-administration of 1.6 mg piroxicam with 15.9 mg cimetidine / kg. b.wt. twice daily for five consecutive days .
6.1. Piroxicam :
Following a single intravenous injection of 1.6 mg piroxicam /kg.b.wt. in 4 normal goats , piroxicam could be detected in a therapeutic concentration, 12 hours post - intravenous dose with a value equal to 4.45 μg/ml. The plasma concentration - time curve of piroxicam following intravenous injection showed that the drug obayed a two compartments open model . This obsevation indicated that the body was viewed as consisting of two - compartments : a compartment of plasma and rapid equilibrating tissues, and a deeper slower equilibrating compartment. The plasma concentrations of piroxicam in 4 normal and 4 arthritic goats following a single and repeated intramuscular injection of 1.6 mg/kg.b.wt. twice daily for five consective days, peaked 4 hours after each intramuscular dose with a lower significant values recorded in arthritic goats than in normal goats . This observation might be attributed to the higher penetrating power of the drug to the inflammed tissues. The mean peak urine concentrations of piroxicam were reached 4 hours after each intramuscular dose with lower significant values in arthritic goats than in normal goats , and 2 hours post - intravenous injection in normal goats . This observation might be attributed to the higher penetrating power of the drug to the inflammed tissues .
Piroxicam clearance showed lower significant values at variable times in arthritic goats than in normal goats after single and repeated intramuscular injections .
The ratio between piroxicam clearance from blood of goats to creatinine clearance decreased with variable significant values at different times in arthritic goats than in normal goats after intramuscular injection and this ratio increased gradually till 2 hours post -intravenous injection in normal goats . These observations indicated that glomerular filtration seemed to be the main pathway of piroxicam elimination with a limited rate of tubular reabsorption .
The highest concentratio of piroxicam in milk reached 6 hours after each intramuscular dose with lower significant values in arthritic goats than in normal goats and 4 hours after intravenous injection in normal goats. This observation might be altributed to accumulation of drug in inflammed tissues . The experimental and therotical milk/plasma concentration ratio of piroxicam showed a low penetration of piroxicam from blood to milk than its passage from blood to urine .
The mean systemic bioavailability of piroxicam following a single intramuscular injection in normal goats was 62.10% . This value refered a better absorption of piroxicam from its site of intramuscular administration .
The synovial fluid concentrations of piroxicam at 4 hours post injection of first, fifth and ninth dose were significantly higher in arthritic goats than normal goats .
6.2. Cimetidine :
Following a single intravenous injection of 15.9 mg cimetidine / kg.b.wt. in normal goats , cimetidine could be detected over 24 hours. The blood concentration - time curve of cimetidine following a single intravenous injection showed that the drug obeyed a two -compartments open model . This indicated that the body was viewed as consisting of two compartments . The mean peak urine concentrations of cimetidine were reached 4 hours post - intramuscular injection with a value of 67.60 ug/ml and 2 hours post - intravenous injection normal goats with a value of 115.65 ug/ml .
The rate of cimetidine clearance increased 6 hours after each dose and then decrease gradually during multiple intramuscular dosage regimen in normal goats . On the other hand cimetidine clearance increased 2 hours post-intravenos injection and then decreased in a
variable rates over 12 hours .
The ratio between cimetidine clearance from blood of goats to
creatinine clearance increased 8 hours after intramuscular dose, and 2 hours post - intravenous injection in normal goats. This ratio was decreased with variable rates over 12 hours . Comparison of cimetidine clearance and creatinine clearance in goats showed that glamerular filtration seemed to be the way of elimination of cimetidine with a variable rates of tubular reabsorption .
The highest concentrations of cimetidine in milk were recorded 4 hours post intramuscular injection and 4 hours post - intravenous injection. The significantly increased with repeating the dose in normal goats as a result of drug accumulation. The experimental and therotical milk blood concentration ratio of cimetidine after intramuscular and intravenous injection showed a low penetration of cimetidine from blood to milk in comparison to its passage from blood to urine .
The calculated systemic bioavailability percent of cimetidine after a single intramuscular injection in normal goats was 79.29%. The value refered a better absorption of cimetidine from its site of intramuscular administration . The disposition kinetic of piroxicam following single intravenous co-administration of piroxicam with cimetidine revealved significant lower values of distribution phase (a), distribution half - life [to.5030] volume of distribution than those values obtained from administration of piroxicam alone. Piroxicam when co-administered with cimetidine was eliminated with half - life [to.5(p)] higher than when piroxicam
given alone. Piroxicam was clear following combination with cimetidine by all clearance processes in the body at slower rate than following administration of piroxicam alone .
Following a single and repeated intramuscular co-administration of 1.6 mg piroxicam with 15.9 mg cimetidine / kg.b.wt. twice daily for the consecutive days in 4 normal and 4 arthritic goats, plasma concentrastions of piroxicam were significantly increased compared with those administered piroxicam alone . This might be attributed to the inhibition of metabolism of piroxicam by cimetidine which lead to a accumlation of piroxicam in blood . The mean peak urine concentrations of piroxicam were reached 4
hours after each intramuscular dose and 2 hours post - intravenous injection piroxicam with cimetidine, and there was significant lower values when piroxicam co-administered with cimetidine compared with
those administered piroxicam alone .
The rate of piroxicam clearance from blood of goats was
significantly decrease in normal and arthritic goats when piroxicam co-administered with cimetidine compared with those administered piroxicam alone. This observation might be attributed to the reduction in hepatic blood flow after cimetidine therapy . The ratios bettween piroxicam clearance to creatinine clearance decreased with variable significant ratios when piroxicam co-administered with cimetidine compared with those administered piroxicam alone. These indicated that the glomerular filtration rate seemed to be the main pathway of
piroxicam elimination .
Concentrations of piroxicam in milk in normal and arthritic goats
increased significantly at most times of sampling after piroxicam -cimetidine therapy compared with those administered piroxicam alone. Therotical milk / plasma concentration ratio of piroxicam revealed low penetration of the durg from blood to milk . The calculated bioavailability of piroxicam in normal goats
following a single intramuscular co-administration of piroxicam with cimetidine was more significantly than bioavailability of piroxicam in
normal goats following single intramuscular injection of piroxicam alone .
The synovial fluid concentrations of piroxicam following co-administration of piroxicam with cimetidine in normal and arthritic
goats were increased significantly more than those recorded in the goats administered piroxicam alone.