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Abstract
Summary:- The current study was undertaken to investigate the pharmacokinetic profile of cefotaxime and side effects after single injection of its therapeutic dose 15 mg /kg b.wt, injected intravenously or intramuscularly in 10 female goats.
Cefotaxime is a third generation cephalosporin which has gained increased use in Veterinary Medicine for treatment of bacterial infection in recent years.
Cefotaxime has many desirable properties that include , broad spectrum of anti- bacterial activity, low incidence of adverse effects and high resistance to penicillinase. These properties have made Cefotaxime valuable.
Ten apparently healthy, 8 month old female goats weighing about 20kg / each goat were used. They were kept in a healthy building under hygienic conitions for one month before the starting of the experiments for acclimatization.
Goats were fed balanced, non – medicated commercial rations and also on green feed.
Ten goats were used for pharmacokinetic studies after they classed to two equal groups. The first group was injected intravenously and the another injected intramuscularly by cefotaxime 15 mg/kg b.wt.
Blood samples were taken from jugular vein after injection by 5 , 10 , 20 , 30 minutes and after 1,2,3,6,12,24,48 and 72 hours.
Liver and kidney samples were taken from two goats from each group 72 h. after injection for histopathological studies. Four goats were used for heamatological studies after intramuscular injection for three successive days by cefotaxime 15 mg/kg b.wt. .
The mean cefotaxime serum concentration following a single intravenous injection in a dose of 15 mg/kg-1 b.wt. in goats was 385.0 + 1.02 µg/ml-1 5 minute post injection then decreased gradually reaching 0.45 + 0.01 µg/ml-1 3 hours post injection . The drug serum concentration declines in a biphasic pattern that can be described by two compartment model.
Cefotaxime was rapidly distributed as evidenced by high value of distribution rate constant (α) (8.22 + 0.75h-1) and short distribution half life (t1/2 α) (10.084 + 0.007 h). The drug was eliminated with elimination rate constant (Kel of 5.290 + 0.455h-1 and elimination half life (t1/2β) was 0.582 + 0.22h. The drug was cleared from the body by a total clearance (CL 1/2 tot) of 0.114 + 0.008L.K.-1 .h-1 .
Cefotaxime was rapidly distributed from the central compartment to the peripheral one at rate constant K12 of 2.273 + 0.427h-1 and highly distributed in different tissues indicated by higher value of Vd area (0.096 + 0.06 L.Kg-1) and Vdss (0.046 + 0.009L.Kg-1). The K12 / K21 ratio was 1.229 . The AUC was 131.105 + 9.16 µg/ml.h-1, AUMC was 55.25 + 21.24µg/ml.h-1 and the mean residence time (MRT) was 0.421+ 0.13h, following i.v injection of cefotaxime at a dose of 15mg/kg-1 in goats.
The mean cefotaxime serum concentration following a single intramuscular injection in a dose of 15mg/kg-1 b.wt. in goat was also detected . The drug was determined in a concentration of 10.0 + 0.21 µg/ml-1 at 5 minutes after injection which increased gradually reaching 80.0µg/ml-1 (observed maximum) concentration) at 0.5 hour after injection. The concentration then declined gradually to become 0.65 µg/ml-1 at 7 hours post injection and it could not be detected at 8 hours after injection.
Cefotaxime displayed absorption rate constant (Kab) of 0.08 + 3.012h-1 and the absorption half life ( t 1/2 ab) was 0.467 + 5.310 h. The peak serum concentration (Cmax) was 77.6 + 6.133 µg/ml-1 reached T max of 0.5 + 0.0123h. The drug elimination half life (t 1/2 el) was 0.65 + 0.031h. The mean resident time (MRT) was 0.403 + 6.113h and the systemic bioavailability (F%) was 76.94% following I.M. injection of cefotaxime in a dose of 15mg/kg-1 body weight .
Cefotaxime evoked non significant changes in erythrocytes count and haemoglobin concentration. A significant increases in packed cell volume (PCV%) and total leukocytic count (WBCs) were observed 5 minutes, 72 hours, one week and two week after first injection. There was a marked increase in neutrophils lymphocytes and monocytes count but associated with in-significant changes in eosinophils and basophils count.
Liver sections, of female goat treated with cefotaxime showed focal distortion of hepatic architecture and central vein. Congestion of hepatic blood vessels and sinusoids was detected. The portal area displayed severe congestion of portal vein and few lymphocytes infiltration. Moderate periportal vacuolar and hyDROPic degenerations were observed. Hemorrhages and Kupffer cell hyperplasia were also detected.
Kidney sections showed different retrogressive changes in the tubular epithelium, including cloudy swelling, vacuolar and hyDROPic degenerations. Hemorrhages, congestion of the renal blood vessels, and perivascular edema were detected. Almost all the cortical renal tubules were dilated with granular eosinophilic material. The cytoplasm of some renal tubules revealed hyaline DROPlet. The glomeruli appeared hypercellular and lobulated with dilated Bowman’s capsule. Subcapsular and interstitial aggregations of lymphocytes were noticed. Focal coagulative necrosis was also visualized.