Pharmacokinetic evaluation of enrofloxacin in chickens.

1. The pharmacokinetics and bioavailability of enrofloxacin in chickens were investigated following intravenous, intramuscular, subcutaneous and oral administration of 10 mg/kg body weight. A rapid distribution phase was followed by a slower elimination phase. 2. The apparent volume of distribution was 2.2 l/kg. Absorption half lives were 0.37, 0.36 and 0.92 h; elimination half lives were 4.06, 4.48 and 4.29 h and bioavailabilities were 87.5%, 80.8% and 59.6% after intramuscular, subcutaneous and oral administration, respectively. The drug completely disappeared from all tissues after 3 days following oral administration. 3. Based on the bioavailability and disposition kinetics of enrofloxacin, administration of one dose per day should both be practical and adequate to maintain plasma enrofloxacin concentrations within the pharmacologically active but lower than tolerance limit.

Kinetic behaviour of sulphaquinoxaline and amprolium in chickens.

The pharmacokinetics of sulphaquinoxaline and amprolium hydrochloride were studied in Hubbard broiler chickens. Single doses of sulphaquinoxaline (100 mg/kg b. wt.), and amprolium hydrochloride (30 mg/kg b. wt.) were administered orally and intravenously to the same birds with 15 days interval between treatments. Sulphaquinoxaline and amprolium HCl were determined colorimetrically. Following i.v. administration, the concentration-time curve of sulphaquinoxaline and amprolium could be explained by a two compartments open model with a t1/2 alpha of 0.16 +/- 0.008 h; 0.17 +/- 0.09 h; t1/2 beta of 12.6 +/- 0.32 h, 4.89 +/- 0.3 h respectively. The total body clearance were 0.278 +/- 0.013 ml/kg/min; 0.562 +/- 0.015 ml/kg/min; volume of distribution at steady state were 0.44 +/- 0.009 L/kg, 0.34 +/- 0.005 L/kg and systemic bioavailability following oral administration were 72.65 +/- 3.38, 66.09 +/- 4.9 percent for sulphaquinoxaline and amprolium HCl respectively. Following oral administration of sulphaquinoxaline and amprolium (the same previous doses) the peak plasma concentrations (Cmax) were 107.8 +/- 1.49 micrograms/ml; 42.9 +/- 1.11 micrograms/ml and occurred at 5.56 +/- 0.1 h, 3.67 +/- 0.05 h respectively. Pharmacokinetic parameters after repeated oral daily administrations of sulphaquinoxaline and amprolium revealed that the Cmax was 184 +/- 1.02 micrograms/ml, and 55.19 +/- 0.35 micrograms/ml at 7.36 +/- 0.18 h and 5.17 +/- 0.15 h and the biological half lives were 1.67 +/- 0.057 h and 1.11 +/- 0.14 h respectively. Sulphaquinoxaline and its N4 acetyl metabolite disappeared from all body tissues at 120 hours, however amprolium persisted in most tissues for 72 hours after the last dose of repeated administrations.

Serum concentrations and tissue residues of spectinomycin in chickens.

Following a single intramuscular injection of 40 mg spectinomycin/kg.b.wt. in normal chickens, a maximum serum concentration was recorded at one hour, with half-lives of absorption [t0.5(ab)] and elimination [t0.5(beta)] valued with 0.21 h and 3.27 h respectively. Following a single intravenous injection of 40 mg spectinomycin/kg b. wt. in normal chickens, the drug obeyed a three compartments open model. The mean systemic bioavailability following intramuscular injection was 3.72 %. The highest serum concentration of spectinomycin was achieved after one hour post each intramuscular dose during multiple dosage regimen. Serum and tissue concentrations of spectinomycin in slaughtered normal chickens following repeated intramuscular administration, three times daily for five consecutive days were investigated. In the present study, spectinomycin was bound in vitro with normal chicken serum protein at a level equal to 5.4 %.

Effect of dietary protein content on nalidixic acid disposition in chickens.

The effect of a diet high in protein (HP) (26%) or low protein (LP) (15%) content on kidney function and pharmacokinetic of nalidixic acid was studied in chickens. Nalidixic acid was given intravenously and orally in a dose of 25 mg/kg b. wt. with 15 days rest period between treatments. Nalidixic acid was determined by microbiological assay. The serum nalidixic acid concentrations were consistently higher in chickens that received a LP diet. The intravenous pharmacokinetics could be described by two compartments model with a t0.5(alpha) 0.13 +/- 0.008 hours and 0.17 +/- 0.008 hours; t0.5(beta) 3.07 +/- 0.07 hours and 2.56 +/- 0.05 hours; Cltot. 0.51 +/- 0.005 ml/kg/min and 0.59 +/- 0.01 ml/kg/min; Vdss 0.349 +/- 0.008 L/kg and 0.462 +/- 0.01 L/kg in LP and HP respectively. This suggests that the protein content of the diet modifies the distribution of body water and kidney function. Also, the results cleared higher recoveries of nalidixic acid in HP chickens.

Influence of diazinon and deltamethrin on reproductive organs and fertility of male rats.

The effect of diazinon and deltamethrine at two dosage levels on male reproductive tissues was studied. The tested doses were given orally to male rats for 65 consecutive days. Sex organs weight analysis, semen picture, testosterone levels and the conception rate were the criteria used to evaluate the productive efficiency of the treated rats. Both doses of diazinon and deltamethrine decreased the weights of most genital organs and motility associated with an increase in the percentage of dead and morphologically abnormal spermatozoa of treated rats. A decrease in the plasma testosterone level was observed in all treated groups. Oral administration of diazinon and deltamethrine for 65 consecutive days decreased the conception rate in non-treated females (mated with treated male).

Effect of garlic on lead contents in chicken tissues.

Lead has been indicted to be involved in the aetiology of human and animal diseases. In view of earlier literature indicating that garlic antagonized lead toxicity, we have investigated the possible use of garlic feeding to clean up lead contents from chickens which had been exposed to natural or experimental lead pollution and consequently eliminate one of the sources of lead pollution to human consumers. Groups of chickens (10 birds each) were given lead alone (lead acetate equivalent to 5 mg lead/kg B.W.) or both lead and garlic simultaneously or lead followed by garlic post-treatment or garlic alone or distilled water. Lead concentrations were reduced in muscle and liver tissues of chickens given both lead and garlic simultaneously or as a post-treatment. Reduction in tissue-lead concentrations were greater in birds given garlic as a post-treatment than those given garlic simultaneously with lead. The results indicate that garlic contain chelating compounds capable of enhancing elimination of lead. Garlic feeding can be exploited to safeguard human consumers by minimizing lead concentrations in meat of food animals which had been grown in a lead polluted environment.

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.

Blood and tissue concentrations of trimethoprim following its administration alone and in combination with josamycin.

Following a single oral dose of trimethoprim (10 mg/kg b. wt.) in normal fowls, the highest serum concentration achieved 4 hours post-administration with value of 0.64 microgram/ml. The absorption half-life time was 0.64 hours. The elimination half life was 4.73 hours. During repeated oral administration of 10 mg/kg b. wt., once daily for five consecutive days, trimethoprim peaked in serum, 4 h after each dose. Trimethoprim persisted in all fowl's tissues for 96 hours after stopping of drug administration. After oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) in normal fowls, a maximum serum concentration of trimethoprim was recorded at 2 hours with half-life of absorption (t0.5(ab)) valued 0.74 hour. The elimination half-life (t0.5 beta) was 4.37 hours. During repeated oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) once daily for five consecutive days in normal fowls, the highest plasma concentrations of trimethoprim occurred 2 hours post each dose. The daily maximum plasma concentrations during the repeated oral administration of both tested drugs were nearly constant.

Pharmacokinetics and tissue residues of josamycin in fowls.

Josamycin is a macrolide antibiotic which is produced by fermentation of cultures of Streptomyces narbonensis. It was once administrated (18 mg/kg b. wt.) in fowls via intravenous, oral and intramuscular routes for determination of blood concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time-curve indicated a two compartments open model with an elimination half life value (t1/2 beta) of 1.83 +/- 0.06 hours. Both oral and intramuscular routes showed higher values, i.e. 2.33 +/- 0.13 and 2.85 +/- 0.17 hours. The lower apparent volume of distribution of Josamycin in fowls than one liter/kg elucidate higher distribution in blood than in tissues. Systemic bioavailability after both oral and intramuscular administration, i.e. 33.88 +/- 2.4 and 27.28 +/- 1.46% respectively, showed lower absorption from site of i.m. application. Josamycin was administered (18 mg/kg b. wt.) intramuscularly and orally once daily for 5 consecutive days. The drug peaked in serum 1 hour (intramuscular) and 2 hours (orally) after each dose. The recorded results revealed that serum level of Josamycin was higher after oral application (29.98 +/- 1.92 micrograms/ml) than after i.m. application. The drug persisted in the lung tissues and fat for 72 hours after administration and disappeared from all body tissues 96 hours after the last dose of repeated administration.

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.