Pharmacokinetics of cefquinome in goats after intramuscular administration alone and with meloxicam

Background: Nonsteroidal anti-inflammatory drugs and antibiotics are commonly prescribed together. We aimed to study the kinetic profile of cefquinome (2 mg/kg b.wt.) following intramuscular administration of it alone and co-administered with meloxicam (0.2 mg/kg b.wt.) in goats.Methods: Five Egyptian Baladi goats, each goat was injected intramuscularly at the dose rate of 2 mg/kg b.wt. Cefquinome into the deep gluteal muscle of hindquarter alone and then after fifteen days washout period, these animals also injected intramuscularly at the dose rate of 2 mg/kg b.wt. Cefquinome preceded with meloxicam at the dose rate of 0.2 mg/kg b.wt. The serum concentrations of cefquinome were detected by high performance liquid chromatography, two compartment model.Results: Following a single dose intramuscular administration of cefquinome alone, peak plasma concentration (1.71±0.0189 μg/ml) was obtained at 1.59±0.0038 h. The absorption half-life (t1/2ab), total body clearance (Cltot), elimination half-life (t1/2el) and area under curve (area under concentration (AUC(0-inf)) of cefquinome were 0.4±0.0028 h, 0.068±0.78 l/h/kg, 9.21±0.178h and 29.36±0.78 µg.h.ml-1, respectively. Following a single dose intramuscular co-administration of cefquinome and meloxicam, peak plasma concentration (1.60±0.0124 μg/ml) was obtained at 1.49±0.0092 h. The absorption half-life (t1/2ab), total body clearance (Cltot), elimination half-life (t1/2el) and area under curve (AUC(0-inf)) of cefquinome were 0.396±0.006 h, 0.094±0.25 l/h/kg, 6.5±0.221 h and 21.38±0.696 µg/h/ml, respectively. Non significant alters were reported in the parameters following co-administration of Cefquinome with meloxicam.Conclusions: From our results, may be concluded that intramuscular administration of meloxicam may be successfully co-administrated with cefquinome for combating bacterial infections with an inflammatory condition in goats without any antagonistic effect

Influence of Flunixin on the Disposition Kinetic of Cefepime in Goats

The pharmacokinetic profile of cefepime (10 mg/kg b.w.) was studied following intravenous and intramuscular administration of cefepime alone and coadministered with flunixin (2.2 mg/kg b.w.) in goats. Cefepime concentrations in serum were determined by microbiological assay technique using Escherichia coli (MTCC 443) as test organism. Following intravenous injection of cefepime alone and in combination with flunixin, there are no significant changes in the pharmacokinetic parameters. Following intramuscular injection of cefepime alone and in combination with flunixin, the maximum serum concentration was significantly increased in flunixin coadministered group compared with cefepime alone. However, no significant changes were reported in other pharmacokinetic parameters. The result of in vitro protein binding study indicated that 15.62% of cefepime was bound to goat's serum protein. The mean bioavailability was 92.66% and 95.27% in cefepime alone and coadministered with flunixin, respectively. The results generated from the present study suggest that cefepime may be coadministered with flunixin without change in dose regimen. Cefepime may be given intramuscularly at 12 h intervals to combat susceptible bacterial infections

Influence of Flunixin on the Disposition Kinetic of Cefepime in Goats

The pharmacokinetic profile of cefepime (10 mg/kg b.w.) was studied following intravenous and intramuscular administration of cefepime alone and coadministered with flunixin (2.2 mg/kg b.w.) in goats. Cefepime concentrations in serum were determined by microbiological assay technique using Escherichia coli (MTCC 443) as test organism. Following intravenous injection of cefepime alone and in combination with flunixin, there are no significant changes in the pharmacokinetic parameters. Following intramuscular injection of cefepime alone and in combination with flunixin, the maximum serum concentration was significantly increased in flunixin coadministered group compared with cefepime alone. However, no significant changes were reported in other pharmacokinetic parameters. The result of in vitro protein binding study indicated that 15.62% of cefepime was bound to goat’s serum protein. The mean bioavailability was 92.66% and 95.27% in cefepime alone and coadministered with flunixin, respectively. The results generated from the present study suggest that cefepime may be coadministered with flunixin without change in dose regimen. Cefepime may be given intramuscularly at 12 h intervals to combat susceptible bacterial infections

Embryotoxic and Teratogenic Effects of Norfloxacin in Pregnant Female Albino Rats

This study was designed to investigate the possible developmental teratogenicity of norfloxacin in rats. Forty pregnant female rats were divided into four equal groups. Group A received norfloxacin in a dose of 500 mg/kg·b·wt/day orally from 6th to 15th day of gestation. Groups B and C received 1000 and 2000 mg/kg·b·wt/day orally for the same period, respectively; Group D behaved as control and received 0.5 mL distilled water orally for the same period. The dams were killed on 20th day of gestation and their fetuses were subjected to morphological, visceral, and skeletal examinations. Norfloxacin significantly decreased the number of viable fetuses, increased the number of resorbed fetuses, and induced retardation in growth of viable fetuses; some visceral and skeletal defects in these fetuses were seen and these effects were dose dependant. Conclusively, norfloxacin caused some fetal defects and abnormalities, so it is advisable to avoid using this drug during pregnancy

Comparative pharmacokinetics of cefoperazone following intravenous and intramuscular administration in goats

AbstractThe pharmacokinetic profile of cefoperazone was studied in goats following intravenous and intramuscular administration of 20mg/kg body weight. Cefoperazone concentrations in serum were determined by microbiological assay technique using Escherichia coli (ATCC 10536) as test organism. Following i.v. administration, the cefoperazone serum concentration–time curve was best fitted in a two compartment open model. Cefoperazone has moderate distribution in the body of goats with Vdss of 0.44±0.03L/kg. The elimination half-life (T0.5(β)), area under curve (AUC) and total body clearance (Cltot) were 1.97±0.14h, 149.63±8.61μgml−1h−1, and 2.17ml/min/kg, respectively. Following i.m. administration, the drug was very rapidly absorbed, with an absorption half-life (T0.5(ab)) of 0.12±0.01h. The maximum serum concentration (Cmax) of 30.42±3.53μgml−1 was attained at (Tmax) 0.58±0.02h, with an elimination half-life (T0.5(el)) of 2.53±0.11h. The systemic bioavailability of cefoperazone in the goats after i.m. administration was 83.62% and in vitro protein binding was 20.34%. The serum concentrations of cefoperazone along 12h post i.m. injection in this study were exceeding the MIC of different susceptible micro-organisms responsible for serious disease problems. Consequently, a suitable intramuscular dosage regimen for cefoperazone was 20mg/kg repeated at 12h intervals in goats. The drug was detected in urine up to 12 and 18h following i.v. and i.m. administration, respectively

Comparative Pharmacokinetics of Cefquinome (Cobactan 2.5%) following Repeated Intramuscular Administrations in Sheep and Goats

The comparative pharmacokinetic profile of cefquinome was studied in sheep and goats following repeated intramuscular (IM) administrations of 2 mg/kg body weight. Cefquinome concentrations in serum were determined by microbiological assay technique using Micrococcus luteus (ATCC 9341) as test organism. Following intramuscular injection of cefquinome in sheep and goats, the disposition curves were best described by two-compartment open model in both sheep and goats. The pharmacokinetics of cefquinome did not differ significantly between sheep and goats; similar intramuscular dose rate of cefquinome should therefore be applicable to both species. On comparing the data of serum levels of repeated intramuscular injections with first intramuscular injection, it was revealed that repeated intramuscular injections of cefquinome have cumulative effect in both species sheep and goats. The in vitro serum protein-binding tendency was 15.65% in sheep and 14.42% in goats. The serum concentrations of cefquinome along 24 h after injection in this study were exceeding the MICs of different susceptible microorganisms responsible for serious disease problems. These findings indicate successful use of cefquinome in sheep and goats

Tigecycline and Gentamicin-Combined Treatment Enhances Renal Damage: Oxidative Stress, Inflammatory Reaction, and Apoptosis Interplay

Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg/kg), TG14 (tigecycline, 14 mg/kg), GM (gentamicin, 80 mg/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity