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

Apramycin was administered to chickens orally, intramuscularly and intravenously to determine blood concentration, kinetic behaviour, bioavailability and tissue residues. Single doses of apramycin at the rate of 75 mg kg-1 body weight were given to broiler chickens by intracrop, i.m. and i.v. routes. The highest serum concentrations of apramycin were reached 0.20 and 0.76 hours after the oral and i.m. doses with an absorption half-life (t1/2(ab.)) of 0.10 and 0.19 hours and an elimination half life (t1/2(beta)) of 1.22 and 2.31 hours respectively. The systemic bioavailability was 2.0 and 58 per cent after intracrop and i.m. administration, respectively, indicating poor absorption of the drug when given orally. Following i.v. injection, the kinetics of apramycin was described by a two-compartment open model with a (t1/2(alpha)) of 1.5 hours, (t1/2(beta)) of 2.1 hours. Vd(ss) (volume of distribution) of 4.82 litre kg-1 and C1(B) (total body clearance) of 1.88 litre kg-1 hour-1. The serum protein-binding of apramycin was 26 per cent. The highest tissue concentrations of apramycin were present in the kidneys and liver. No apramycin residues were detected in tissues after six hours except in the liver and kidneys following intracrop dosing and kidneys following i.m. administration.

Effect of pantothenic acid on disposition kinetics and tissue residues of sulphadimidine in chickens.

Sulphadimidine was administered to chickens via the intracrop route to determine plasma concentrations of the unchanged sulphonamide and its acetylated derivatives, kinetic disposition, tissue residues and acetylation. The sulphadimidine was given alone (group 1) at a dose of 200 mg kg-1 bodyweight. Pantothenic acid was given via the intracrop route at a dose of 100 mg kg-1 bodyweight one hour before (group 2) and six hours after (group 3) sulphadimidine administration (200 mg kg-1 bodyweight intracrop). The highest plasma concentrations of sulphadimidine in groups 1, 2 and 3 were reached in 1.73, 1.62 and 1.71 hours, respectively, following intracrop administration. In birds of groups 1, 2 and 3 no sulphadimidine was detected at 72, 24 and 48 hours, respectively, following its administration. Estimation of sulphadimidine in most of the body tissues revealed that all tissues examined had lower concentrations than plasma. In chickens given pantothenic acid (groups 2 and 3) before and after sulphadimidine administration, an increase in the concentration of N4 acetylated derivatives of sulphadimidine was observed compared with birds given sulphadimidine alone (group 1).

Pharmacokinetic profile of cefotaxime in goats.

Cefotaxime was administered to goats intravenously, intramuscularly and subcutaneously to determine blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time curve indicated a two compartment open model, with an elimination half-life value (t1/2 beta) of 22.38 +/- 0.41 minutes. Both intramuscular and subcutaneous routes showed slower values, that is, 38.64 and 69.58 minutes. The apparent volume of distribution of cefotaxime in goats was less than 1 litre kg-1 and suggested a lower distribution in tissues than in blood. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 77.8 +/- 1.7 and 44.0 +/- 0.8 micrograms ml-1 at 29.6 and 40.4 minutes, respectively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1.08 and 1.25 times the intravenous availability, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration.

Effect of subclinical lead toxicity on the immune response of chickens to Newcastle disease virus vaccine.

The effect of lead acetate (20 and 40 mg kg-1 bodyweight daily) administered via the crop from day old to 56 days of age on the immune response to Newcastle disease virus vaccine (NDVV, La Sota strain) was studied in 354 Lohman chickens. Lead decreased the mitogenic response of peripheral blood lymphocytes (PBL) to phytohaemagglutinin-P (PHA-P) in birds vaccinated with NDVV. It also decreased the weights of the bursa of Fabricius, the thymus glands and the spleen relative to bodyweight. Lead administration decreased the antibody titre to NDVV in the vaccinated groups. The percentage mortality due to a challenge with a virulent velogenic Newcastle disease virus was higher in the lead intoxicated birds.

Tissue concentrations and pharmacokinetics of florfenicol in broiler chickens.

Florfenicol was once administered to broiler chickens via i.v., i.m. and oral route (30 mg/kg body weight) to study its plasma concentrations, kinetic behaviour, systemic bioavailability and tissue levels. Following a single i. v. injection, the kinetic disposition of florfenicol followed a two-compartmental open model with an elimination half-life of 172 min, total body clearance of 26.9 ml/kg/min and a steady state volume of distribution of 5.11 litre/kg. The highest plasma concentrations of florfenicol were 3.82 and 3.20 micrograms/ml following single i.m. and oral administration, respectively. The systemic bioavailability was 96.6 and 55.3 per cent after i.m. and oral administration. The plasma protein binding of florfenicol was 18.5%. Following the administration, the highest tissue concentration of the drug was found in kidney, bile, lung, muscle, intestine, heart, liver, spleen and serum. Low concentrations of the drug were found in brain, bone marrow and fat. No florfenicol residues were detected in tissues and serum after 72 h except in the bile, it disappeared after 96 h.

Haemodynamic alterations induced by toxic level of sodium taurocholate.

Haemodynamic effects of sodium taurocholate (S.T.) were studied on isolated guinea pig's auricles, rabbit's heart, rabbit's aortic strip, guinea pig's tracheal chain as well as the blood pressure and ECG pattern changes in pentobarbital anaesthetized dogs. S.T. induced significant negative inotropic and chronotropic effects on the isolated auricles of guinea pig's especially in higher concentrations. Using isolated rabbit's heart, the negative inotropic and chronotropic effects induced by S.T. were found to be depending on the concentration. Cardio-inhibitory actions of the salt are not due to either cholinergic beta 1-adrenergic blocking effect or nicotine like activity. S.T. in all tested concentrations had no effect on the contractile response of isolated rabbit's aortic strip or guinea pig's tracheal chain and did not prevent the contractile response induced by noradrenaline and histamine. In anaesthetized dogs, i.v. injections of the salt in a dose of 30 mg/kg b. wt. produced a significant decrease in systolic and diastolic pressure, but lower doses induced no significant changes. A dose of 30 mg/kg b. wt. of the salt potentiates the decrease in systolic and diastolic pressure when coadministered with the neuromuscular blocking agent, atracurium besylate. Atropine, propranolol and phentolamine did not alter the hypotensive effect of S.T. (neither cholinergic nor beta 1-adrenergic blocking effect). The electrocardiographic pattern induced by S.T. (20-30 mg/kg b. wt.) in dogs were mainly characterized by decrease in heart rate and prolongation of P-T interval.

Influence of sodium taurocholate on the potency and duration of action of some neuromuscular blocking agents.

The effect of sodium taurocholate (S. T.) on the contractile response of rat-phrenic nerve diaphragm, frog's musculus rectus abdominis and frog's musculus gastrocnemius sciatic nerve preparation was studied. Moreover, interaction of S. T. with neuromuscular blockers are carried out, too. S. T. was found to have a dose-dependent reduction in the contractile response of the tested preparation. On the other hand, the inhibitory effect induced by S. T. did not block or alter the stimulatory effect of either acetylcholine or prostigmine. Trials were made to estimate the potency of S. T. in a comparison with other skeletal muscle relaxant drugs. In this respect S. T. exhibited a more potent effect than gallamine. In contrast, other skeletal muscle relaxants (dtubocurarine, atracurium, pancuronium and succinylcholine) were highly potent. There was also a marked synergistic effect between S. T. and other neuromuscular agents.

Comparative haemodynamic alterations induced by pipecuronium and pancuronium.

Haemodynamic effects of pipecuronium bromide (Pi.) and pancuronium bromide (Pa.) were studied on isolated rabbit's heart, guinea pig's tracheal chain as well as the blood pressure in pentobarbital anaesthetized dogs. Pi. induced negative inotropic and chronotropic effects on the isolated rabbit's heart especially in lower concentrations. However, higher concentrations provoked two opposite effects, negative chronotropic and positive inotropic activity. In addition, Pa. in lower concentrations caused positive inotropic and negative chronotropic activity, while higher concentrations induced negative inotropic and chronotropic activity. Cardioinhibitory actions of both tested drugs are not due to either cholinergic or beta 1-adrenergic blocking effect but it may be due to nicotine-like activity. In anaesthetized dogs, i.v. injections of both tested drugs produced a transient decrease in systolic and diastolic pressure in doses above the therapeutic level. This effect may be referred to the partial ganglion blocking effect of both tested drugs.

Pharmacokinetic profile of cefotaxime in goats.

Cefotaxime was once administered in goats via intravenous, intramuscular and subcutaneous routes for determination of blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time curve indicated two compartments open model, with an elimination half-life value (t1/2 beta) of 22.38 +/- 0.41 minutes. Both intramuscular and subcutaneous routes showed lower values i.e. 38.64 and 69.58 minutes. The lower apparent volume of distribution of cefotaxime in goats than one liter/kg elucidated lower distribution in tissues than in blood. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 77.8 +/- 1.7 and 44.0 +/- 0.8 micrograms/ml at 29.6 and 40.4 minutes, respectively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1.08 and 1.25, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration.

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.

Influence of dimethoate on testicular and epididymal organs, testosterone plasma level and their tissue residues in rats.

The effect of dimethoate at two dosage levels (6.25 and 12.50 mg/kg b. wt.) on male reproduction tissues and their tissue residues in rats were studied. The tested doses were given orally to male rats for 65 consecutive days. Sex organs weight analysis, semen picture, testosterone levels and histopathology of the male genital organs were the criteria used to evaluate the reproductive efficiency of the treated rats. There was a dose-related decrease in the weights of most genital organs 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. Histological examination revealed that dimethoate caused testicular lesions characterized by moderate to severe degenerative changes of spermatogonial cells and by partial arrest of spermatogenesis. Sections from liver revealed that the central veins and hepatic sinusoids appeared dilated, with some areas of haemorrhage. The highest concentrations from dimethoate were found in liver and tests and the lowest in skeletal muscle. Dimethoate and its metabolite analog were still present in a detectable concentration 21 days after stopping its oral administration.

Glomerular expression and elevated serum Bcl-2 and Fas proteins in lupus nephritis: preliminary findings.

Programmed cell death (apoptosis) is involved in glomerular injuries leading to glomerulonephritis. Bcl-2 and Fas are proteins that promote cell survival and death, respectively. This study tests the hypothesis that lupus nephritis is associated with alterations of Bcl-2 and Fas protein expression. Thirty-six patients with lupus nephritis and 10 controls (normal individuals) were included in this study. Bcl-2 and Fas positive cells were examined in kidney biopsies by immunohistochemistry. Bcl-2 and Fas serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl-2 and Fas proteins were completely absent. In lupus nephritis patients, glomerular expression of Bcl-2 and Fas was seen in mesangial cells (1.3 +/- 0.1 and 2.0 +/- 0.1 for Bcl-2 and Fas, respectively). Similarly, a statistically significantly higher Bcl-2 (217.1 +/- 85.9) and Fas (767.9 +/- 271) serum levels were found in lupus patients compared to controls (148.6 +/- 87, 550.3 +/- 91 for Bcl-2 and Fas, P < 0.05). A direct correlation between serum Bcl-2 and Fas and chronicity index was also found. Compared to normal controls, lupus nephritis is associated with glomerular expression and elevated serum levels of Bcl-2 and Fas proteins. These findings suggest possible roles for Bcl-2 and Fas in glomerular injury during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic ramifications of our findings are open to further investigation.

Tissue concentrations and pharmacokinetics of florfenicol in broiler chickens.

1. Florfenicol (30 mg/kg body weight) was administered to broiler chickens via intravenous (i.v.), intramuscular (i.m.) and oral routes to study its plasma concentrations, kinetic behaviour, systemic bioavailability and tissue content. 2. Following a single i.v. injection, the kinetic disposition of florfenicol followed a 2-compartmental open model with an elimination half-life of 173 min, total body clearance of 26.9 ml/kg/min and a steady state volume of distribution of 5.11 l/kg. 3. The highest plasma concentrations of florfenicol were 3.82 and 3.20 micrograms/ml following single i.m. and oral administration, respectively. The systemic bioavailability was 96.6% and 55.3% after i.m. and oral administration. The plasma protein binding of florfenicol was 18.5%. 4. Following its administration, the highest tissue concentrations of the drug were found in the kidney bile, lung, muscle, intestine, heart, liver, spleen and plasma. Low concentrations of the drug were found in brain, bone marrow and fat. No florfenicol residues were detected in tissues and plasma after 72 h except in the bile from where it disappeared after 96 h.