Pharmacokinetics,urinary excretion and plasma protein binding of danofloxacin following intravenous administration in buffalo calves (Bubalus bubalis)

Pharmacokinetics, urinary excretion and plasma protein binding of danofloxacin was investigated in buffalo calves following intravenous administration at the dose rate of 1.25 mg/kg to select the optimal dosage regimen of danofloxacin. Drug concentrations in plasma and urine were measured by microbiological assaying. In vitro plasma protein binding was determined employing the equilibrium dialysis technique. The distribution and elimination of danofloxacin were rapid, as indicated by values (mean ±SD) of distribution half-life (t_1/2α = 0.16 ± 0.07 h) and elimination half-life (t_1/2β = 4.24 ± 1.78 h), respectively. Volume of distribution at steady state (Vss) = 3.98 ± 1.69 L/kg indicated large distribution of drug. The area under plasma drug concentration versus time curve (AUC) was 1.79 ± 0.28 μg/mlxh and MRT was 8.64 ± 0.61 h. Urinary excretion of danofloxacin was 23% within 48 h of its administration. Mean plasma protein binding was 36% at concentrations ranging from 0.0125 μg/ml to 1 μg/ml. On the basis of pharmacokinetic parameters obtained, it is concluded that the revision of danofloxacin dosage regimen in buffalo calves is needed because the current dosage schedule (1.25 mg/kg) is likely to promote resistance.     

Acute-phase Response Alters the Disposition Kinetics of Cefepime following Intravenous Administration to Rabbits

The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 × 10⁸ cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 μg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1^°C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level–time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V _dss) and body clearance (CL_tot) were affected in febrile as compared to healthy animals. The mean values of V _dss and CL_tot of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V _dss (0.917 L/kg) and CL_tot (0.205 L/kg per h) of cefepime were significantly lower, whereas t _1/2λ, MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease.     

Effect of induced pyrexia on the disposition kinetics of ciprofloxacin in dogs

Ciprofloxacin was administered intravenously @ 5 mg/kg body weight to six healthy dogs. After a washout period of two weeks, fever was induced by injecting Escherichia (E) coli endotoxin. Ciprofloxacin was administered again. Blood samples were collected at various time intervals and analyzed for ciprofloxacin with HPLC. The kinetic analysis revealed the volume of distribution in healthy vs. febrile dogs as 2.12 ± 0.32 vs. 1.79 ± 0.43 L/Kg, respectively. The elimination half life was 2.23 ± 0.78 and 2.07 ± 0.74 hours in healthy and febrile dogs, respectively. Similarly, dogs under healthy and febrile conditions showed comparable total plasma clearance of 0.66 ± 0.06 and 0.60 ± 0.07 L/Kg/h, respectively. All these and other investigated kinetic parameters were statistically non significant. This study concludes that the pharmacokinetic behavior of ciprofloxacin is similar under healthy and febrile conditions. Thus, the kinetic studies of fluoroquinolones conducted in normal/healthy animals may be used to depict the pharmacokinetic parameters in diseased animals.     

Pharmacokinetic studies of levofloxacin after oral administration in healthy and febrile cow calves

The present experiment was designed to study the pharmacokinetics of levofloxacin in six healthy cross bred female cow calves (4 to 6 months age) weighing between 40 to 80 kg. Plasma from blood was separated by centrifugation at 10,000 rpm. Quantitative estimation of levofloxacin was done by UV-VIS spectrophotometer at 286 nm. The mean maximum plasma concentration (Cp_max ) of levofloxacin in febrile calves (5.28?±?0.32 µg/ml) did not differ significantly as compared with healthy calves (4.50?±?0.22 µg/ml) after single dose (20 mg/kg) oral administration. The mean therapeutic plasma concentration ( Cp_ther ) of levofloxacin was maintained for longer period in febrile calves (10 h) as compared to healthy calves ( 8 h). The mean maximum urine concentration (Cu_max) in febrile (40.86?±?2.19 µg/ml) also did not differ significantly as compared with healthy calves (39.38?±?2.43 µg/ml). No significant difference in various pharmacokinetic parameters of plasma was observed in healthy calves ( β?=?0.23?±?0.01/h ; t1/2 β?=?3.00?±?0.17 h and MRT?=?4.66?±?0.14 h ) and febrile calves ( β?=?0.23?±?0.01/ h; t1/2 β?=?3.05?±?0.16 h and MRT?=?5.04?±?0.14 h ) . The mean value of β, and t ½ β calculated in urine also did not differ between healthy and febrile calves. However, the value of MRT(3.79?±?0.07 h) and Cl_B(1.65?±?0.09 ml/kg/min) calculated in urine of febrile calves significantly(p?B?=?2.09?±?0.13 ml/kg/min). Based on kinetic profile levofloxacin may be given orally at the dose rate of 1.49 mg/kg B.W.at 8 h intervals in febrile calves.     

Bioequivalence Study of Two Long-acting Oxytetracycline Formulations in Sheep

Two commercially available long-acting oxytetracycline hydrochloride formulations (Primamycin LA (Pfizer) and Terralent 20% LA (İ.E. Ulagay)) were administered by the intramuscular route to 20 clinically healthy sheep at a dose of 20 mg/kg. The study was performed in a two-period crossover design. Plasma samples were analysed by high-pressure liquid chromatography. The mean maximum concentrations (C _max) was 8.00 ± 2.05 μg/mland 8.61 ± 1.42 μg/ml, respectively. The mean area under the concentration time curve (AUC) values were 154.95 ± 50.37(μg h)/ml and 161.70 ± 47.02(μg h)/ml, respectively. The 90%confidence intervals for the ratio of C _max and AUC values for the test and reference product are with in the interval 70−143% for C _max and interval 80-−125% for AUC proposed by EMEA. It was concluded that Primamycin LA and Terralent 20% LA formulations are bioequivalent in their rate and extent of drug absorbtion. Ozdemir N. and Yıldırım, M., 2006. Bioequivalence study of two long-acting oxytetracycline formulations in sheep. Veterinary Research Communications, 30(8), 929–934     

Plasma Concentrations,Pharmacokinetics and Urinary Excretion of Gatifloxacin after Single Intravenous Injection in Buffalo Calves

The pharmacokinetics and urinary excretion of gatifloxacin were investigated after a single intravenous injection of 4 mg/kg body weight in buffalo calves. The therapeutic plasma drug concentration was maintained for up to 12 h. Gatifloxacin rapidly distributed from blood to tissue compartments, which was evident from the high values of the distribution rate constant, α₁ (11.1 ± 1.06 h⁻¹) and the rate constant of transfer of drug from central to peripheral compartment, k ₁₂ (6.29 ± 0.46 h⁻¹). The area under the plasma drug concentration–time curve and apparent volume of distribution were 17.1 ± 0.63 (μg.h)/ml and 3.56 ± 0.95 L/kg, respectively. The elimination half-life (t _{1/2 β}), total body clearance (Cl_B) and the ratio of drug present in tissues and plasma (T/P) were 10.4 ± 2.47 h, 235.1 ± 8.47 ml/(kg.h) and 10.1 ± 2.25, respectively. About 19.7% of the administered drug was excreted in urine within 24 h. A satisfactory intravenous dosage regimen for gatifloxacin in buffalo calves would be 5.3 mg/kg at 24 h intervals. Abbreviations for pharmacokinetic parameters are given in the footnote of Table I     

Comparative efficacy of bromocriptine,cabergoline and thyroxine in inducing oestrus in bitches

Forty bitches in anoestrus for more than six months from the last heat, with a serum progesterone level less than 1 ng/ml were subjected to oestrus induction trials using anti-prolactin drugs and levothyroxine, once daily orally for 20 consecutive days. The mean serum progesterone level among them was found to be 0.57 ± 0.03 ng/ml. Out of 10 animals treated in each group, five (50%) in Group I (bromocriptine @ 50 μg/kg body weight), nine (90%) in Group II (cabergoline @ 5 μg/kg body weight), eight (80%) in Group III (thyroxine @10 μg/kg body weight) and seven (70%) in Group IV (thyroxine @ 5 μg/kg body weight) responded by evincing proestrual bleeding. The mean (±SEM) time taken from initiation of treatment to onset of proestrual bleeding in Groups I, II, III and IV was 28 ± 3.39, 13.44 ± 3.12 (P < 0.05), 24.50 ± 3.18 and 33 ± 2.21 days respectively. The mean (±SEM) duration of proestrus and oestrus in the treatment groups was 9.80 ± 0.86, 10.11 ± 0.68, 11.25 ± 0.88 and 10.71 ± 0.68 days and 7.60 ± 0.24, 8 ± 0.29, 8.5 ± 0.63 and 7.85 ± 0.46 days respectively. The conception rate in relation to the number of animals responding to oestrus induction in the treatment groups was 80%, 78%, 63% and 57%, respectively. The mean (±SEM) gestation length calculated from the last breeding date and litter size in the treatment groups varied from 60.50 ± 1.55 to 64.00 ± 0.82 days and 5.14 ± 0.34 to 6.40 ± 0.40 respectively.     

Pharmacokinetic behaviour of enrofloxacin and its metabolite ciprofloxacin after subcutaneous administration in cattle

This study compared pharmacokinetic profiles in cattle dosed subcutaneously with two different formulations of enrofloxacin (5% and 10%) at a dose of 5 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by a HPLC/u.v. method. The pharmacokinetic parameters of enrofloxacin and its metabolite were similar in both injectable formulations. Enrofloxacin peak plasma concentration (5%: 0.73 ± 0.32; 10%: 0.60 ± 0.14 μg/mL) was reached at 1.21 ± 0.52 and 1.38 ± 0.52 h to 5 and 10%, respectively. The terminal half-live and area under curve were 2.34 ± 0.46 and 2.59 ± 0.46 h, and 3.09 ± 0.81 and 2.93 ± 0.58 μg·h/mL, to 5 and 10%, respectively. The AUC/MIC₉₀ and Cmax/MIC₉₀ ratios for both formulations exceed the proposed threshold values for optimized efficacy and minimized resistance development whilst treating infections or septicaemia caused by P. multocida and E. coli.     

Selenium and copper status of camels in Al-Jouf area (Saudi Arabia)

In order to understand the changes in copper and selenium status in camel dam and calf around the calving period, blood samples were collected in 26 she-camel before delivery and after as well as their calves after birth. The mean values for the mother and their newborn were respectively 70.3 ± 19.8 and 58.6 ± 13.9 μg/100 ml for copper, 5.3 ± 3.7 and 4.6 ± 1.7 μg/100 ml for selenium. No change was observed for copper, but selenium increased after parturition in 81% of the case. The selenium status of camel calf was correlated with those of its mother, but not the copper. As the whole the correlation between selenium and copper was significantly positive. The selenium status was improved in camel receiving diet enriched with barley. The maternal transfer to milk has to be investigated.     

Pharmacokinetic-Pharmacodynamic Modelling of Danofloxacin in Turkeys

Colibacillosis is a systemic disease responsible for important economic losses in poultry breeding; fluoroquinolones, including danofloxacin, are used to treat diseased animals. The purpose of the present study was to estimate pharmacokinetic–pharmacodynamic (PK-PD) surrogates for bacteriostasis, bactericidal activity and bacterial elimination against Escherichia coli O78/K80, using a PK-PD approach, for danofloxacin in turkeys after oral administration. Eight healthy turkeys, breed BUT 9, were included in a two-way crossover study. The drug was administered intravenously (i.v.) and orally at a dose rate of 6 mg/kg bw. The values of the elimination half-life and the total body clearance after i.v. administration were 8.64 ± 2.35 h and 586.76 ± 136.67 ml kg^-1h^-1, respectively. After oral administration, the values of the absolute bioavailability and the elimination half-life were 78.37± 17.35% and 9.74± 2.93 h, respectively. The minimum inhibitory concentration against the investigated strain in turkey serum was 0.25 μg/ml, four times higher than in broth. The lowest effective ex vivo AUC₂₄/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coliO78/K80 were 0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the present study could be interpreted as being sufficient to eliminate E. coli with an MIC 0.25 μ g/ml. However, considering the demand that antimicrobial resistance should be avoided by complete bacterial elimination, PK-PD considerations suggest that an even higher dose of 32 mg/kg per day or 0.7 mg/kcal per day should be evaluated in clinical trials.     

Serum sialic acid and oxidative stress parameters changes in cattle with leptospirosis

This study was designed to disclose some indicators of oxidative stress and inflammation in natural cases of bovine leptospirosis. For this purpose, 12 bulls exhibiting clinical signs of leptospirosis and 10 healthy bulls were used. Animals were subjected to thorough clinical examination and the clinical signs were recorded. All animals were blood sampled in order to determine serum total sialic acid (TSA), lipid bound sialic acid (LBSA), malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), uric acid (UA), total protein (TP), albumin and glucose. Urine samples were collected from each animal and examined under dark-field microscope to observe spirochetes. Diseased animals exhibited clinical signs suggesting leptospirosis and the diagnosis was supported by positive dark-field microscope examination. Mean TSA (mmol/L), LBSA (mmol/L), TP (g/dl), albumin (g/dl), glucose (mg/dl), MDA (μmol/L), GSH (mg/dl), NO (nmol/ml), and UA (mg/L) levels were 1.63 ± 0.02, 0.40 ± 0.10, 7.18 ± 0.24, 3.23 ± 0.5, 64.96 ± 1.88, 5.71 ± 0.11, 78.68 ± 0.72, 7.94 ± 0.34, and 8.75 ± 0.41 in healthy bulls, and 2.50 ± 0.05, 0.70 ± 0.2, 9.27 ± 0.17, 2.55 ± 0.62, 107.93 ± 2.52, 8.82 ± 0.14, 47.85 ± 1.85, 14.57 ± 0.63 and 15.85 ± 0.80 in leptospirosis cases, respectively. The differences between the two groups were statistically significant (P < 0.001). Increased TSA, LBSA, MDA, NO, UA, TP, glucose and decreased GSH and albumin concentrations were suggestive of inflammation and oxidative stress in diseased bulls. The results obtained may suggest that oxidative damage along with other mechanisms might have taken part in the pathogenesis of bovine leptospirosis and further detailed studies are needed to fully understand the mechanism(s) of the disease.     

Disposition Kinetics of Difloxacin After Intravenous,Intramuscular and Subcutaneous Administration in Calves

The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration–time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t _1/2β) were 5.56 ± 0.33 h, 6.12 ± 0.42 h and 7.26 ± 0.6 h, respectively. The steady-state volume of distribution (V _dss) was 1.12 ± 0.09 L/kg and total body clearance (Cl_B) was 2.19 ± 0.1 ml/(min. kg). The absorption half lives (t _1/2ab) were 0.38 ± 0.027 h and 2.1 ± 0.09 h, with systemic bioavailabilities (F) of 96.5% ± 6.4% and 84% ± 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C _max) of 3.38 ± 0.13 μg/ml and 2.18 ± 0.12 μg/ml were attained after (t _max) 1.22 ± 0.20 h and 3.7 ± 0.52 h. The MIC₉₀ of difloxacin for Mannheimia haemolytica was 0.29 ± 0.04 μg/ml. The AUC/MIC₉₀ and C _max/MIC₉₀ ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7–36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.     

Plasma pharmacokinetics and milk levels of ceftriaxone following single intravenous administration in healthy and endometritic cows

Pharmacokinetics and milk levels of ceftriaxone were studied in healthy and endometritic cows following single intravenous administration. The drug was detected up to 8 h of dosing in plasma of healthy and endometritic cows and the drug disposition followed three-compartment open model. The values of Vd_area, AUC, t_1/2β, Cl_B, MRT and P/C ratio were 0.50 ± 0.19 L.kg⁻¹, 62.2 ± 23.3 μg.ml⁻¹.h, 1.02 ± 0.07 h, 0.30 ± 0.09 L.kg⁻¹.h⁻¹, 1.55 ± 0.25 h and 0.52 ± 0.27, respectively, in healthy and 1.55 ± 0.52 L.kg⁻¹, 37.0 ± 17.1 μg.ml⁻¹.h, 1.56 ± 0.25 h, 0.56 ± 0.14 L.kg⁻¹.h⁻¹, 2.14 ± 0.34 h and 1.44 ± 0.60, respectively, in endometritic cows. The drug was detected in milk for 36 h after administration. For MIC₉₀ of 0.5 μg.ml⁻¹ the most appropriate dosage for ceftriaxone, would be 9.0 mg.kg⁻¹ repeated at 6 h intervals for the treatment of endometritis in cows.     

Investigation of Immunmodulatory effects of levamisole and vitamin E on Immunity and some blood parameters in newborn Jersey calves

The immunmodulatory effects of dl-α tocopherol (vitamin E) and levamisole on the immune system and some blood parameters of newborn Jersey calves were investigated with the present study. Treatment groups 1, 2 and 3 were injected 13,3 ml isotonic saline solution (0,9% NaCl), 3 mg/kg levamisole HCl and 2000 IU vitamin E weekly, starting at birth until the age of two weeks. Average serum IgM levels of the control, levamisole and vitamin E calves were 111,7 ± 9,3 mg/100 ml, 251,9 ± 27,6 mg/100 ml, 202,2 ± 43,3 mg/100 ml respectively on day 22. Average serum IgG levels of the levamisole and vitamin E groups elevated, compared to the control group on days 1, 8, 15 and 22. However, there were stastistically differences in treatment and control groups for serum total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and cortisol values and whole blood counts. All differences were in the reference ranges. Levamisole and vitamin E could be used as an alternative way for their beneficial effects such as improving the humoral immune responses of calves and their safety and practical use against the neonatal period infections in the field.     

Erythrocyte Lipid Peroxides and Blood Zinc and Copper Concentrations in Acute Undifferentiated Diarrhoea in Calves

Undifferentiated acute calf diarrhoea is a major concern for the dairy industry and its aetiopathogenesis remains diverse. The present study aimed to examine the role of oxidative stress through estimation of erythrocyte lipid peroxide levels and blood zinc and copper concentrations using natural cases of diarrhoea in calves aged 15–30 days old. The calves were kept under identical managemental conditions and were provided with pooled whole colostrum during the first three days and thereafter with only whole milk until they were 1 month old. Diarrhoeic (n = 11) and normal calves (n = 11) of the same age group (15–30 days old) were randomly selected from an organized dairy farm for the study. The mean blood zinc concentration (50.01±2.45 μmol/L vs 66.06±3.06 μmol/L) was significantly (p < 0.05) lower and copper concentration was significantly (p < 0.05) higher in diarrhoeic calves (12.90±0.31 μmol/L vs. 9.44±0.16 μmol/L) than in the healthy calves. The erythrocyte lipid peroxides level was higher (p < 0.05) in diarrhoeic calves (6.88±0.23 nmol malondialdehyde (MDA) per mg of haemoglobin (Hb)) than healthy calves (6.27±0.07 nmol MDA per mg Hb). From the results of the study it is concluded that oxidative stress and antioxidant minerals (zinc and copper) might play important roles in the aetiopathogenesis of bovine calf diarrhoea.     

Plasma Disposition and Faecal Excretion of Netobimin Metabolites and Enantiospecific Disposition of Albendazole Sulphoxide Produced in Ewes

Netobimin (NTB) was administered orally to ewes at 20 mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high-performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of albendazole sulphoxide (ABZSO) enantiomers produced was also determined. Neither NTB nor albendazole (ABZ) was present and only ABZSO and albendazole sulphone (ABZSO₂) metabolites were detected in the plasma samples. Maximum plasma concentrations (C<_max) of ABZSO (4.1 ± 0.7 μg/ml) and ABZSO₂ (1.1 ± 0.4 μg/ml) were detected at (t _max) 14.7 and 23.8 h, respectively following oral administration of netobimin. The area under the curve (AUC) of ABZSO (103.8 ± 22.8 (μg h)/ml) was significantly higher than that ABZSO₂(26.3± 10.1 (μg h)/ml) (p<0.01). (−)−ABZSO and (+)-ABZSO enantiomers were never in racemate proportions in plasma. The AUC of (+)-ABZSO (87.8±20.3 (μg h)/ml) was almost 6 times larger than that of (−)−ABZSO (15.5 ±5.1 (μg h)/ml) (p < 0.001). Netobimin was not detected, and ABZ was predominant and its AUC was significantly higher than that of ABZSO and ABZSO₂, following NTB administration in faecal samples (p > 0.01). Unlike in the plasma samples, the proportions of the enantiomers of ABZSO were close to racemic and the ratio of the faecal AUC of (−)−ABZSO (172.22 ±57.6 (μg h)/g) and (+)-ABZSO (187.19 ±63.4 (μg h)/g) was 0.92. It is concluded that NTB is completely converted to ABZ by the gastrointestinal flora and absorbed ABZ is completely metabolized to its sulphoxide and sulphone metabolites by first-pass effects. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver that are responsible for sulphoxidation and sulphonation of ABZ.     

Bacteria flora and heavy metals in cultivated oysters <Emphasis Type="Italic">Crassostrea iredalei</Emphasis> of Setiu Wetland,East Coast Peninsular Malaysia

Slipper oyster Crassostrea iredalei is a species of good demand for its sweet flavor and white coloured flesh. The filter feeding nature predisposes oysters to accumulation of pathogenic and heavy metals in waters impacted by sewage pollutions and may thus render the oysters unfit for human consumption. A study was undertaken to investigate the presence of bacteria flora and heavy metal concentrations in cultivated oysters Crassostrea iredalei at Setiu Wetland, Terengganu, the only source of cultivated oysters in East Coast of Malaysia. A total of 200 slipper oyster samples were analyzed. The bacteria were isolated using non selective agar such as TSA agar and selective agars before they were then identified using conventional methods in combination with BBL Crystal identification kit. Heavy metals such as zinc (Zn), copper (Cu), cadmium (Cd), and lead (Pb) concentrations were determined using atomic absorption spectrophotometry. Results showed that the oysters harbor predominantly Shewanella putrifaciens followed by Vibrio parahaemolyticus, Vibrio vulnificus, Vibrio cholerae, Enterobacter cloacae, Escherichia coli and Chromobacterium violaceum. They also contain high concentration of Zn (785.68 ± 285.88 μg/g) with the lowest heavy metal was Pb (0.17 ± 0.15 μg/g), whilst the concentrations of other heavy metals were Cu (38.9 ± 13.2 μg/g) and Cd (1.60 ± 0.28 μg/g). The study is very useful to evaluate the type of bacteria and heavy metal present in oyster meat for human consumption.     

Pharmacokinetics of Tilmicosin (Provitil Powder and Pulmotil Liquid AC) Oral Formulations in Chickens

A bioavailability and pharmacokinetics study of powder and liquid tilmicosin formulations was carried out in 18 healthy chickens according to a single-dose, two-period, two-sequence, crossover randomized design. The two formulations were Provitil and Pulmotil AC. Both drugs were administered to each chicken after an overnight fast on two treatment days separated by a 2-week washout period. A modified rapid and sensitive HPLC method was used for determination of tilmicosin concentrations in chicken plasma. Various pharmacokinetic parameters including area under plasma concentration–time curve (AUC₀₋₇₂), maximum plasma concentration (C _max), time to peak concentration (t _max), elimination half-life (t _1/2β), elimination rate (k _el), clearance (Cl_B), mean residence time (MRT) and volume of distribution (V _d,area) were determined for both formulations. The average means of AUC₀₋₇₂ for Provitil and Pulmotil AC were very close (24.24 ± 3.86, 21.82 ± 3.14 (μg.h)/ml, respectively), with no significant differences based on ANOVA. The relative bioavailability of Provitil as compared to Pulmotil AC was 111%. In addition, there were no significant differences in the C _max (2.09 ± 0.37, 2.12 ± 0.40 μg/ml), t _max (3.99 ± 0.84, 5.82 ± 1.04 h), t _1/2β (47.4 ± 9.32, 45.0 ± 5.73 h), k _el (0.021 ± 0.0037, 0.022 ± 0.0038 h⁻¹), Cl_B (19.73 ± 3.73, 21.37 ± 4.54 ml/(min/kg)), MRT (71.20 ± 12.87, 67.15 ± 9.01 h) and V _d,area (1024.8 ± 87.5, 1009.8 ± 79.5 ml/kg) between Pulmotil AC and Provitil, respectively. In conclusion, tilmicosin was rapidly absorbed and slowly eliminated after oral administration of single dose of tilmicosin aqueous and powder formulations. Provitil and Pulmotil AC can be used as interchangeable therapeutic agents.     

Pharmacokinetic Profile of Erythromycin after Intramammary Administration in Lactating Dairy Cows with Specific Mastitis

The pharmacokinetics of erythromycin was studied in five lactating dairy cows following single intramammary infusion of 300 mg erythromycin in each of two quarters per cow with specific mastitis. Levels of erythromycin in plasma and quarter milk samples were measured by agar plate diffusion assay using Micrococcus luteus (ATCC 9341) as the test organism. Erythromycin level in plasma reached a peak concentration value (C _max) of 0.07 ± 0.01 μg/ml at 30 min; thereafter, levels declined gradually to reach 0.05 ± 0.00 μg/ml 12 h post drug administration. The pharmacokinetic profile of the drug revealed mean absorption half life (t _1/2ka) as 0.26 ± 0.05 h. The drug was eliminated slowly with elimination half-life (t _1/2β) of 13.75 ± 0.35 h and elimination rate constant (k _el) of 0.04 ± 0.00 h⁻¹. The volume of distribution based on the zero-time plasma concentration intercept of the least-squares regression line of the elimination phase (V _d(B)) was 0.032 L/kg. The drug crossed to untreated quarters also; mean drug levels of 0.20 ± 0.07, 0.23 ± 0.07, 0.17 ± 0.04, and 0.17 ± 0.04 μg/ml were found at 3, 6, 8 and 12 h, respectively. The mean drug concentration for treated quarters was measured as 22.97 ± 2.31 μg/ml milk at first milking (12 h) following drug infusion. No apparent adverse reaction was seen in cows administered erythromycin. It is concluded that following intramammary infusion erythromycin diffuses readily and extensively in various body fluids and tissues and adequate concentration is maintained in udder tissues for at least 12 h post intramammary administration. Thus, erythromycin may be recommended for local therapy of acute mastitis caused by Gram-positive bacteria in lactating dairy cows.     

The curative and antioxidative efficiency of ivermectin and ivermectin + vitamin E-selenium treatment on canine <Emphasis Type="Italic">Sarcoptes scabiei</Emphasis> infestation

The objective of the present study was to investigate the curative and antioxidative efficacy of ivermectin and ivermectin + vitamin E-selenium, and the influence of these agents on oxidative stress parameters in canines infested by Sarcoptes scabiei. Twenty two sarcoptic mites infested dogs and nine healthy dogs of 6 months to 2 years of age were divided into three groups. Group I comprised of healthy dogs (n = 9) whereas animals in group II (n = 11) and III (n = 11) were positive for scabies. Group II animals were treated with only 1% ivermectin @ 0.2 mg/kg SC whereas group III were additionally treated with Vitamin E and selenium (tocopherol 50 mg + Se 1.5 mg/ml) @0.5 ml/20 kg IM at weekly intervals for three times. Blood samples were collected on day 0 and 28 post therapy. The values for hemato-biochemical parameters and activities of antioxidant enzymes were significantly decreased (P < 0.05) whereas level of lipid peroxidation was significantly increased in all the infested dogs in comparison to the healthy dogs on day 0 which approached normalcy by day 28 post therapy. The dogs of group III showed better clinical recovery in comparison to group II at the end of therapy. Thus, administration of vitamin E and selenium in addition to standard therapy can alleviate these alterations hastening the clinical recovery of diseased dogs and can be recommended as an adjunct therapy with miticides for canine sarcoptic mange.