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Biomedical subjects

M Atef

Publications and source records attributed to M Atef.

At least 19 recordsLinked to original sources

Influence of aflatoxin B1 on the kinetic disposition, systemic bioavailability and tissue residues of doxycycline in chickens.

1. Disposition kinetics of doxycycline (doxy) was studied in healthy chickens and chickens experimentally intoxicated with aflatoxin B1 by intravenous, oral or intramuscular (i.m.) injection, in a single dose of 15 mg/kg body weight. In addition, the tissue distribution and residual pattern of the drug were determined in healthy and intoxicated chickens. 2. The maximum serum concentrations of doxy were reached 1.97 and 2.37 h after oral, and 1.57 and 2.92 h after i.m. dosage in healthy and aflatoxic birds, respectively. 3. The volumes of distribution and total body clearances were higher in aflatoxic birds (1.75 l/kg and 14.61 ml/kg/min) than in healthy chickens (0.93 l/kg and 4.6 ml/kg/min). Data relating to intravenous injection were analysed using a two-compartment open model curve fit. 4. Lower values of systemic bioavailability were observed in intoxicated birds (30.9 and 33.9%) than healthy ones (43.7 and 57.3%) after oral and i.m. administration, respectively. 5. The highest concentration of doxy residues were present in liver, kidney and serum followed by heart and muscles. Doxy residue concentrations in edible tissues was below the EEC limit 6 d after cessation of oral or i.m. medication with 15 mg/kg body weight twice daily for 5 successive days.

Administration, Oral↗

Pharmacokinetics of difloxacin in goats.

The pharmacokinetic properties of difloxacin following intravenous (i.v.) and intramuscular (i.m.) administration in goats were investigated. Difloxacin was administered in a single dose of 5 mg/kg body weight for both routes and was assayed in biological fluids (serum and urine) to determine its concentrations, kinetic behaviour and systemic availability. Following a single i.v. injection, the serum difloxacin level was best approximated to follow a two-compartment open model using weighted non-linear regression analysis. The elimination half-life (t1/2 beta) was 6.3 +/- 0.11 h. The volume of distribution at steady-state (Vdss) was 1.1 +/- 0.012 L/kg and the total body clearance (Cltot) was 0.13 +/- 0.001 L/kg/h. Following a single i.m. administration, difloxacin was rapidly absorbed and the mean peak serum concentration (4.1 +/- 0.23 micrograms/ml) was achieved 1 h post administration. The extent of serum protein binding of difloxacin in goats was 13.79 +/- 1.02% and the systemic availability was 95.4 +/- 1.17%. Following i.m. injection of difloxacin at a dose rate of 5 mg/kg b.wt for 5 consecutive days, the drug could not be detected in serum and urine at 4th day from the last injection.

Animals↗

Some pharmacokinetic data for danofloxacin in healthy goats.

The pharmacokinetics of danofloxacin was determined in five clinically normal adult female goats after intravenous (IV) or intramuscular (IM) doses of 1.25 mg/kg body weight. Blood and urine samples were collected from each animal at precise time intervals. Serum and urine concentrations were determined using microbiological assay methods and the data were subjected to kinetic analysis. After intravenous injection, the serum concentration time curves of danofloxacin were characteristic of a two-compartment open model. The drug was rapidly distributed and eliminated with half-lives of 17.71 +/- 1.38 min and 81.18 +/- 3.70 min, respectively. The drug persisted in the central, highly perfused organs with a K12/K21 ratio of 0.67 +/- 0.25. The mean volume of distribution at a steady state (Vdss was 1.42 +/- 0.15 L/kg. After intramuscular administration, the serum concentration peaked after 0.58 +/- 0.04 h at approximately 0.33 +/- 0.01 microg/ml. While danofloxacin could be detected in serum for 4 and 6 h, it was recovered in urine for up to 24 and 72 h after IV and IM administration, respectively. The systemic bioavailability after IM injection was 65.70% +/- 10.28% and the serum protein-bound fraction was 13.55 +/- 1.78%.

Animals↗

Disposition kinetics of florfenicol in goats by using two analytical methods.

Florfenicol, a monofluorinated analogue of thiamphenicol, has antibacterial activity against a broad spectrum of bacterial strains, including enteric bacteria that are resistant to chloramphenicol and thiamphenicol. The pharmacokinetics of florfenicol was studied following a single intravenous bolus or intramuscular injections at a dose of 20 mg/kg body weight, in five healthy goats. Serum florfenicol concentrations were determined using two analytical methods: microbiological assay and high-performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using redundant routine equations and the results derived from each method were compared. While florfenicol was detected for up to 4 and 8 h after administration by the bioassay, the drug was recovered in serum after 12 and 24 h by HPLC following intravenous and intramuscular injections, respectively. Comparison of the concentration profiles obtained by the two methods revealed substantial differences in the resultant kinetic data. Values for the initial serum concentration, elimination half-life, the area under the serum concentration-time curve, the mean residence time, and the systemic bioavailability were significantly (P < 0.01) higher when florfenicol concentrations were determined using HPLC. In conclusion, differences between analytical methodologies should be considered when interpreting the kinetic data for clinical use. However, both the hepatic biotransformations and the interchangeability of enantiomers need further investigation.

Animals↗

Pharmacokinetic properties of florfenicol in Egyptian goats.

The single-dose disposition kinetics of florfenicol was determined in healthy, non-lactating Egyptian goats, after its intravenous (i.v.) and intramuscular (i.m.) administration at 20 mg kg-1 b.wt. Drug concentrations in serum and urine were determined using microbiological assay method and data was subjected to a kinetic analysis. Florfenicol concentrations in serum decreased in a bi-exponential manner after intravenous administration with distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives of 10.256 +/- 0.938 and 56.237 +/- 3.102 minute, respectively. The steady-state volume of distribution (Vdss) and total body clearance (Cltot) were 3.413 +/- 0.304 l kg-1 and 3.306 +/- 0.333 l kg h-1. After intramuscular administration, the peak serum concentration (Cmax) was 0.859 +/- 0.025 micrograms ml-1, achieved at (Tmax) 1.220 + 0.045 h. Florfenicol was detected in urine up to 24 and 96 hour after i.v. and i.m. administration, respectively. The extent of the protein binding and systemic bioavailability of florfenicol were 22.45 +/- 1.727% and 65.718 +/- 3.372%, respectively.

Animals↗

Elimination of tilmicosin in lactating ewes.

Tilmicosin was injected subcutaneously to lactating ewes once at a dose of 10 mg kg-1 b.wt. to determine its plasma, milk, urine and ruminal juice concentrations. Tilmicosin could be detected in all those fluids 30 minutes after injection. Milk and urine concentrations were higher than those of plasma and ruminal juice. The drug was detectable in milk, urine and plasma for 9, 4 and 3 days after injection, respectively. No amount of tilmicosin could be detected in ruminal juice 12 hours following administration. The mean peak concentration of tilmicosin in plasma and milk (Cmax) were 1.29 and 9.5 micrograms ml-1 and were obtained at (Tmax) 5.235 and 15.093 hours, respectively. The drug was slowly eliminated from plasma and milk as indicated by its long half-life (t1/2el) of 15.4 and 26.2 hours, respectively. The mean binding of tilmicosin to plasma and milk proteins in vitro was 16.8% and 26.8%, respectively. The drug was not bound to ruminal juice at any extent. The rate of tilmicosin renal clearance revealed that it was correspondingly increased with higher blood concentrations. While creatinine clearance showed no significant change after tilmicosin administration. The ratio (fractional clearance) between tilmicosin renal clearance to creatinine clearance was less than one indicating that the glomerular filtration is the main pathway of elimination through kidneys. The rate of ruminal gas fermentation in ewes was inhibited after subcutaneous injection of tilmicosin at a dose of 10 mg kg-1 b.wt. The tested samples taken at different time intervals from the rumen of ewes showed a subsequent reduction in the rate of fermentation as compared to control samples. The reduction was correspondingly increased with the increase of tilmicosin concentration in ruminal juice and returned to normal thereafter.

Animals↗

Influence of Phoxim on testicular and seminal vesicle organs, testosterone and cholinesterase level and its tissue residues in male rats.

The effect of Phoxim (Volaton) at two dosage levels (23 and 46 mg/kg b.wt.) on male reproduction tissues and their residues in rats were studied. The tested doses were given orally to male rats for 60 consecutive days. Sex organs weight analysis, semen picture, testosterone and cholinestrase enzyme (ChE) levels, histochemistry, histopathological changes and mating trials were the criteria used to evaluate the reproductive efficiency of the treated rats. There was a dose-related decrease in the weights of testicles and sperm motility associated with an increase in the percentages of dead and morphologically abnormal spermatozoa of treated rats. A decrease in plasma testosterone levels was observed in the treated groups. Histopathological examination revealed that phoxim caused testicular lesions characterized by moderate to severe degenerative changes of spermatogonial cells and by partial arrest of spermatogenesis. Plasma, brain and testicular ChE levels were reduced in treated rats. Phoxim and its oxygen analog concentrations were progressively increased by the time of exposure and represented double fold in liver as compared to that in skeletal muscles and testicles. The histochemical examination of testicles of treated rats showed a marked decreament in the ChE activity in tunica albuginea and sperms. A decrease in this enzyme was also noticed in liver hepatocytes, granular layer of the cerebral cortex and medulla of suprarenal gland.

Abnormalities, Drug-Induced↗

Interaction between lead toxicity and some sulphonamides in rabbits: effect on certain blood constituents and serum enzymes.

Two main equal groups of clinically healthy, non pregnant rabbits were classified into 4 subgroups (5 rabbits each). The 1st and 2nd subgroups were treated with sulphaquinoxaline or sulphadiazine in a single oral dose of 100 mg/kg b. wt., while the 3rd and 4th subgroups received a repeated oral dose of 100 mg/kg b. wt., daily for 5 successive days, respectively. The second main group received lead acetate in a dose of 4.2 mg/kg b. wt. per day for 2 months, then was classified as in case of the 1st main group and administered the respective sulphonamides in their recommended doses. The experimental lead intoxication was found to decrease the free delta-aminolevulinic acid dehydratase (delta-ALA-D) activity in blood of lead intoxicated rabbits after 4 and 8 weeks. Also, the ratio of free and with glutathione reactivated delta-ALA-D was increased 2.9 and 2.2 after 4 and 8 weeks, respectively as compared with before lead administration (1.19), indicating toxicity. The sulphonamide/creatinine ratio was increased after administration of both sulphonamides but higher in lead intoxicated rabbits as compared with healthy ones. The AST/ALT ratio was decreased 4 and 8 weeks after lead exposure. The AST, ALT and AST/ALT ratio, alkaline phosphatase, urea and creatinine were not altered in healthy rabbits. Repeated oral administration of sulphadiazine caused a significant increase in serum AST, ALT, alkaline phosphatase and creatinine level in healthy and lead intoxicated rabbits. On the other hand, AST/ALT ratio in both healthy and lead intoxicated rabbits was found to decrease 1 h after the last dose as compared with before treatment.

Animals↗

Disposition kinetics of cephradine in normal and Escherichia coli infected goats.

The pharmacokinetics of cephradine was studied following single and repeated intramuscular injections in normal and Escherichia coli infected goats. Bioavailability of cephradine was determined in normal goats after a single intramuscular dose. The serum concentrations of cephradine following a single and repeated intramuscular administration of 10 mg/kg b.wt. twice daily for five consecutive days, peaked 2 hours after each intramuscular dose with a lower significant value recorded in E. coli infected goats than in normal goats. The absorption half-lives (t0.5(ab)) following a single intramuscular injection of cephradine was significantly higher in E. coli infected goats (1.18 h) than in normal goats (0.64 h). The elimination half-lives (t0.5(beta)) of cephradine were significantly higher in E. coli infected goats than in normal goats following the administration of fifth and ninth doses. The urine and milk concentrations of cephradine were significantly lower in E. coli infected goats than in normal goats. The mean systemic bioavailability of cephradine following a single intramuscular injection in normal goats was 73.9%.

Animals↗

Kinetic disposition, systemic bioavailability and tissue distribution of salinomycin in chickens.

Salinomycin was administered to chickens orally and intravenously to determine blood concentration, kinetic behaviour, bioavailability and tissue residues. The drug was given by intracrop and intravenous routes in a single dose of 20 mg kg-1 body-weight. The highest serum concentrations of salinomycin were reached half an hour after oral dosage with an absorption half-life (t0.5(ab)) of 3.64 hours and elimination half-life (t0.5(beta)) of 1.96 hours. The systemic bioavailability percentage was 73.02 per cent after intracrop administration, indicating the high extent of salinomycin absorption from this route in chickens. Following intravenous injection the kinetics of salinomycin can be described by a two-compartment open model with a t1/2(alpha) of 0.48 hours, Vd ss (volume of distribution) of 3.28 litre kg-1 and Cl(beta) (total body clearance) of 27.39 ml kg-1 min-1. The serum protein-binding tendency of salinomycin as calculated in vitro was 19.78 per cent. Salinomycin concentrations in the serum and tissues of birds administered salinomycin premix (60 ppm) for two weeks were lower than those after administration of a single intracrop dose of pure salinomycin (20 mg kg-1 bodyweight). The highest concentration of salinomycin residues were present in the liver followed by the kidneys, muscles, fat, heart and skin. No salinomycin residues were detected in tissues after 48 hours except in the liver and these had disappeared completely by 72 hours.

Absorption↗

Effect of pyridoxine on the distribution of chloramphenicol and its residues in the chicken.

1. Chickens were given either a single dose of chloramphenicol (50 mg/kg body weight per os) or a dose of chloramphenicol together with pyridoxine (25 mg/kg per os) given 1 h before or 4 h afterwards. 2. Concentrations of chloramphenicol were determined in samples of serum and the rates of distribution and elimination extrapolated. Concentrations of chloramphenicol in muscle, liver and kidney were also determined. 3. Serum concentrations of chloramphenicol were lower in chickens given both pyridoxine and chloramphenicol compared with those given only chloramphenicol. 4. Differences were most pronounced during the post-absorptive phase. The rates of disappearance of chloramphenicol residues from tissues were enhanced by pyridoxine. 5. The biological half life of chloramphenicol and area under the concentration-time curve were both reduced by the concurrent administration of pyridoxine. 6. Availability of pyridoxine may be a rate limiting factor in the biotransformation of xenobiotics, though its indiscriminate use could cause failure of antibiotic therapy.

Absorption↗

Pharmacokinetic profile and tissue distribution of monensin in broiler chickens.

1. The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. 2. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 h, volume of distribution of 4.11 l/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 h after intracrop dosage with an absorption half-life of 0.27 h and an elimination half life of 2.11 h. The systemic bioavailability was 65.1% after intracrop administration. Serum protein-binding tendency of monensin calculated in vitro was 22.8%. 3. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin premix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 h after oral administration. The highest concentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 h after the last oral dose. No monensin residues could be detected in tissues after 48 h, except in liver which cleared completely by 72 h.

Animals↗

Comparison of gentamicin toxicity in normal and diabetic rats.

Gentamicin treatment caused an elevation in serum urea and creatinine concentrations and ALT activity, associated with pathological changes in the liver and kidney. The pathological and blood chemistry changes were more severe in diabetic gentamicin-treated than in non-diabetic gentamicin-treated rats. Alloxan-diabetic rats had lowered blood glutathione concentrations which may have been responsible for the enhancement of gentamicin toxicity in these rats.

Animals↗

Influence of E. coli infection on the disposition kinetic of nalidixic acid in broiler chickens.

The pharmacokinetic data of nalidixic acid were investigated in normal and E. coli infected chickens. The highest serum concentration were reached after 2 hours with t0.5 (ab) of (1.706 +/- 0.1 min in normal and 2.030 +/- 0.11 min in diseased) and (1.72 +/- 0.11 min in normal and 1.416 +/- 0.044 in diseased chickens) following oral and intramuscular administration, respectively. The elimination half-life t0.5 (beta) were (2.514 in normal and 2.35 hr in diseased) and (2.567 hr in normal and 2.672 hr in diseased) respectively. Following intravenous injection the kinetic of nalidixic acid followed two compartments open model with t0.5 of (6.27 and 9.15 hr), Vd (0.45 and 0.79 L/kg), Cltot (8.86 and 13.32 ml/kg/min) in normal and E. coli infected chickens, respectively. Administration of nalidixic acid twice daily for 5 successive days in a dose level of 25 mg/kg b. wt. by oral and intramuscular routes showed a cumulative behaviour.

Administration, Oral↗

Pharmacotoxicological aspects of nitrate and nitrite in domestic fowls.

1. The effects of nitrates and nitrites on growth, erythrocytic count, liver and kidney functions, humoral and cell mediated immune responses in cockerels were investigated. 2. Sodium nitrate (4.2 g/kg diet) and sodium nitrite (1.7 g/kg) retarded growth, caused methaemoglobinaemia and changes in erythrocytic count, serum concentrations of glutamic-pyruvic transaminase, creatinine and urea. 3. Cockerels given nitrate or nitrite in the food had reduced haemagglutination responses after injection of sheep erythrocytes and a reduced delayed hypersensitivity reaction to purified protein derivative tuberculin following sensitisation to Bacille Calmette Guerin. 4. Nitrates and nitrites are environmental pollutants present in food and water and they may contribute to the aetiology of liver and kidney diseases and problems related to failure of immunity in domestic fowls.

Alanine Transaminase↗

Pharmacokinetics of chloramphenicol in normal and Escherichia coli infected chickens.

1. Disposition kinetics were compared in healthy chickens and in chickens naturally infected with E. coli following the intravenous, intramuscular and oral administration of chloramphenicol in a single dose of 20 mg/kg body weight. 2. Lower serum chloramphenicol concentration in diseased chickens were reported after intravenous injection, but they were higher than normal 30 min after intramuscular and oral administration. Following intravenous injection the volume of distribution was increased in diseased chickens. 3. The biological half-life in normal chickens was 8.32 +/- 0.5 h and was prolonged in diseased birds (26.21 +/- 0.2 h). The body clearance of chloramphenicol was reduced in diseased chickens. 4. The rate of absorption of chloramphenicol was delayed after administration via the oral route but the extent of absorption was increased. The maximum concentration was higher and it was reached after a longer time in diseased than in normal chickens after administration by both intramuscular and oral routes.

Administration, Oral↗

Enhanced diabetogenic effects of combined treatment with hydrochlorothiazide and prednisone in adjuvant arthritic rats.

Adjuvant arthritic rats received either hydrochlorothiazide (HCT) alone, prednisone (PR) alone, both drugs, or vehicle. HCT combined with PR enhanced the extent of hyperglycemia, hyperlipidemia, hypercholesterolemia, and elevation of serum urea concentration and glutamic pyruvic transaminase activity observed when either drug was given alone. These results suggest that administration of thiazide diuretics to treat edema encountered during anti-inflammatory steroid therapy may increase the risk of diabetes mellitus, atherosclerosis and certain thrombotic disorders. HCT did not reduce the anti-inflammatory activity of PR.

Alanine Transaminase↗

Disposition of tylosin in goats.

The disposition kinetics of tylosin was studied in goats after intravenous or intramuscular injection of 15 mg/kg b. wt. Following i.v. injection, tylosin was rapidly and widely distributed in goats (half life of distribution: 0.2 h and volume of distribution: 1.7 l/kg). It was slowly eliminated with a mean elimination half life of 3.04 h and a total body clearance rate of 6.8 ml/kg/min. Following i.m. injection, tylosin was slowly absorbed (T1/2ab of 1.82 h). Tylosin concentration in serum was greater than 1 microgram/ml after 1 h and persisted up to 12 h post-injection. The peak concentration (Cmax, 2.38 micrograms/ml) was obtained after 4.19 h. The systemic bioavailability of tylosin injected intramuscularly was 72.6% and the serum protein bound fraction was 37.6% of the total drug. Tylosin was excreted in milk and urine at concentrations much higher than that in serum. Low concentrations of tylosin were reported in ruminal juice of goats. In conclusion tylosin should be injected every 15 hours to obtain an appreciable concentration in serum, milk and urine.

Absorption↗