Subcutaneous pharmacokinetics and dosage regimen of cefotaxime in buffalo calves (Bubalus bubalis)

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 ± 0.52 µg/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination half-life were 0.173 ± 0.033 h and 1.77 ± 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 ± 0.10 l/kg and 0.45 ± 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 ± 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.     

Pharmacokinetics, urinary excretion and dosage regimen of levofloxacin following a single intramuscular administration in cross bred calves

The pharmacokinetics and urinary excretion following single intramuscular administration of levofloxacin at a dose of 4 mg/kg was investigated in seven male cross bred calves. Appreciable plasma concentration of levofloxacin (0.38 ± 0.06 µg/ml) was detected at 1 min after injection and the peak plasma level of 3.07 ± 0.08 µg/ml was observed at 1 h. The drug level above MIC₉₀ in plasma was detected up to 12 h after administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.14 ± 0.24 /h). The overall systemic bioavailability of levofloxacin, after intramuscular administration, was 56.6 ± 12.4%. The high value of AUC (7.66 ± 0.72 mg . h/ml) reflected the vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was noted by the high value of Vd_area (1.02 ± 0.05 l/kg). The high ratio of AUC/MIC (76.6 ± 7.25) obtained in this study indicated excellent clinical and bacteriological efficacy of levofloxacin in calves. The elimination half-life and MRT were 3.67 ± 0.4 h and 5.57 ± 0.51 h, respectively. The total body clearance (Cl_B) was 204.9 ± 22.6 ml/kg/h. On the basis of the pharmacokinetic parameters, a suitable intramuscular dosage regimen for levofloxacin in calves would be 1.5 mg/kg repeated at 12 h intervals.     

Disposition kinetics,urinary excretion and dosage regimen of kanamycin in buffalo calves following single intravenous administration

The disposition kinetics and appropriate dosage regimen for kanamycin were investigated in buffalo calves following a single intravenous dose of 10 mg/kg body weight. The distribution and elimination half-lives were 0.12±0.01 h and 1.94±0.11 h, respectively. The apparent volume of distribution and total body clearance were 0.2±0.01 L/kg and 92.9±3.69 ml/kg/h, respectively. About 74% of the administered dose was excreted in urine in 24 h. A suitable dosage regimen for the intravenous administration of kanamycin was also calculated.Abbreviation SEM standard error of the mean     

Pharmacokinetics and dosage regimen of cefotaxime in cross-bred calves following single intramuscular administration

The pharmacokinetics, penetration into erythrocytes and plasma protein binding of cefotaxime were investigated in cross-bred calves. Following a single intramuscular dose of cefotaxime (10 mg/kg), the absorption half-life and elimination half-life were 0.13±0.03 h and 2.97±0.72 h, respectively. The apparent volume of distribution and total body clearance were 3.28±0.72 L/kg and 0.78±0.08 L/kg per h, respectively. The extent of penetration into erythrocytes was 24–40% of the total blood concentration. Cefotaxime was bound to plasma proteins of calves to the extent of 25.5–33.6%. A satisfactory intramuscular dosage regimen for cefotaxime in calves would be 11 mg/kg followed by 10 mg/kg at 7 h intervals.Abbreviations ATCC American type cell culture - MIC minimum inhibitory concentration - PCV packed cell volume     

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.     

Pharmacokinetics of lincomycin following single intravenous administration in buffalo calves

Lincomycin 10 mg kg^?1, IV in buffalo calves followed two-compartment open model with high distribution rate constant α (11.2?±?0.42 h^?1) and K ₁₂/K ₂₁ ratio (4.40?±?0.10). Distribution half-life was 0.06?±?0.01 h and AUC was 41.6?±?1.73 μg mL^?1 h. Large Vd_area (1.15?±?0.03 L kg^?1) indicated good distribution of lincomycin in various body fluids and tissues. Peak plasma level of lincomycin (71.8?±?1.83 μg mL^?1) was observed at 1 min as expected by IV route. The elimination half-life and MRT of lincomycin were short (3.30?±?0.08 and 4.32?±?0.11 h, respectively). Lincomycin 10 mg kg^?1 IV at 12-h interval would be sufficient to maintain T?>?MIC above 60 % for bacteria with minimum inhibitory concentrations (MIC) values ≤1.6 μg mL^?1. Favourable pharmacokinetic profile in buffalo calves and a convenient dosing interval suggest that lincomycin may be an appropriate antibacterial in buffalo species for gram-positive and anaerobic bacterial pathogens susceptible to lincomycin.     

Characterization of TLR4 signaling in water buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>)

Lipopolysaccharide (LPS) treatment of Peripheral Blood Mononuclear Cells (PBMC) isolated from the water buffalo resulted in the activation of TLR signaling intermediates as supported by the western blot of pERK. Activation of ERK resulted in phosphorylation of IκB-α which lead to its degradation which in turn followed by nuclear translocation of NF-κB, which is also supported by the western blot analysis. The nuclear translocation of NF-κB culminated in the induction of mRNA expression of TNF-α. Thus this study demonstrates the TLR signaling in PBMCs of water buffalo which is as similar to that reported earlier in mice and human beings.     

Disposition kinetics and dosage regimen of sulfapyridine in buffalo (Bubalus bubalis).

The disposition kinetics and dosage regimen of sulfapyridine were studied in buffalo calves following a single intravenous dose of 100 mg/kg. Distribution half-life (t1/2 alpha) elimination half-life (t1/2 beta) and Vd (area) was 0.181 +/- 0.008 h, 13.4 +/- 0.52 h and 0.59 +/- 0.03 L kg-1, respectively. Total body clearance, which represents the sum of all clearance processes, and tissue/plasma (T/P) ratio were calculated to be 31.1 +/- 2.28 ml kg-1 h-1 and 2.25 +/- 0.09, respectively. A satisfactory intravenous dosage regimen of sulfapyridine in buffalo would be 104 mg/kg followed by 75 mg/kg at 24 h intervals.     

Disposition kinetics of gentamicin following repeated parenteral administration in buffalo calves (Bubalus bubalis).

Disposition kinetics of gentamicin was determined in buffalo calves following repeated parenteral administration of 5 mg/kg body weight. The absorption (t1/2 Ka) and elimination half-life (t1/2 beta) were found to be 0.40 +/- 0.12 and 4.33 +/- 0.39 h, respectively. Statistical comparison of the values of pharmacokinetic determinants generated in this study with the corresponding values following single intramuscular injection at the same dose level as reported earlier by GARG and GARG, 1990, revealed that the consecutive administration of drug influenced the pharmacokinetics profile of gentamicin. Elimination half-life was significantly longer (P < 0.05). Since elimination rate constant value was significantly reduced, the subsequent dosage will have to be reduced particularly if kidney functions are not normal. Otherwise, dosage regimen need not be changed.     

Pharmacokinetics and urinary excretion of gentamicin in Bubalus bubalis calves following intramuscular administration

The pharmacokinetics and urinary excretion of gentamicin was studied in buffalo calves after a single intramuscular administration (10 mg kg-1). Kinetic determinants were calculated by using a two compartment open model. The absorption (t1/2Ka) and biological half lives (t1/2 beta) were calculated to be 0.43 +/- 0.08 and 3.79 +/- 0.23 h, respectively. The value of the apparent volume of distribution (VdB) was found to be 0.38 +/- 0.07 litre kg-1. The satisfactory intramuscular dosage regimen of gentamicin for buffalo calves would be 3.23 mg kg-1 as priming dose and 2.88 mg kg-1 as maintenance dose to be repeated at 12 hour intervals to achieve and maintain the therapeutic plasma levels within safe limits. Urinary excretion of gentamicin was very rapid during the first 12 hours as 48.07 +/- 1.39 per cent of the total administered dose was excreted unchanged during this period.     

The kinetic disposition and dosage regimen for carbenicillin in buffalo calves

The distribution half-life, elimination half-life, apparent volume of distribution and total body clearance of carbenicillin in healthy buffalo calves following a single intravenous administration (50 mg/kg) were 0.057±0.005 h, 1.688±0.11 h, 0.185±0.021 L kg^-1 and 75.97±6.519 ml kg^-1 h^-1 respectively. A satisfactory dosage regimen for carbenicillin in buffalo calves was calculated to be 56 mg/kg followed by 52 mg/kg body weight repeated at 6 h intervals.     

Pharmacokinetics following intravenous administration and pharmacodynamics of cefquinome in buffalo calves

Disposition following single intravenous injection (2 mg/kg) and pharmacodynamics of cefquinome were investigated in buffalo calves 6–8 months of age. Drug levels in plasma were estimated by high-performance liquid chromatography. The plasma concentration–time profile following intravenous administration was best described by a two-compartment open model. Rapid distribution of cefquinome was evident from the short distribution half-life (t _½α ?=?0.36?±?0.01 h), and small apparent volume of distribution (Vd_area?=?0.31?±?0.008 L/kg) indicated limited drug distribution in buffalo calves. The values of area under plasma concentration–time curve, elimination half-life (t _½β ), total body clearance (Cl_B), and mean residence time were 32.9?±?0.56 μg·h/mL, 3.56?±?0.05 h, 60.9?±?1.09 mL/h/kg, and 4.24?±?0.09 h, respectively. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cefquinome were 0.035–0.07 and 0.05–0.09 μg/mL, respectively. A single intravenous injection of 2 mg/kg may be effective to maintain the MIC up to 12 h in buffalo calves against the pathogens for which cefquinome is indicated.     

Blood Biochemical and Ruminal Liquor Profile in Buffaloes (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Showing Omasal Impaction

The blood biochemical and ruminal fluid parameters of 5 buffaloes showing omasal impaction were studied, together with 10 healthy buffaloes as control. The diseased buffaloes had significantly higher serum aspartate aminotransferase, bilirubin, glucose, blood urea nitrogen, creatinine, total protein, globulin and fibrinogen levels and significantly lower plasma calcium, potassium and chloride concentrations than the controls. The ruminal liquor of the diseased buffaloes revealed characteristic physical, chemical and microbial changes and had significantly higher methylene blue reduction time and ammonia-nitrogen level.     

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were C_max 6.93 ± 0.58 μg/ml, T_max 0.5 hr, t_½kα 0.16 ± 0.05 hr, t_½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.     

Prevalence of antibodies against Bubaline herpesvirus (BuHV-1) among Mediterranean water buffalo (Bubalus bubalis) with implications in buffalo trade

Background: Both Bovine herpesvirus (BoHV-1) and Bubaline herpesvirus (BuHV-1) have been reported to cross the species barrier. Antibody seroconversion in glycoprotein E (gE) blocking ELISA during BuHV-1 infection has been documented. Recent diagnostic efforts have focused on the development and application of discriminatory tests to distinguish between infections with BoHV-1 and BuHV-1.

Objective: To evaluate the impact and distribution of these two infections in water buffalo farms in two regions (Piedmont (n = 3) and Campania (n = 10), Italy) where infectious bovine rhinotracheitis control programs have been implemented.

Animals and methods: Sampling was carried out on 13 buffalo farms comprising 1089 animals using specific gE-indirect ELISA's test able to discriminate among BoHV-1 and BuHV-1 infections.

Results: 59.0% of animals reacted positive to ELISA (irrespective of whether BoHV-1 or BuHV-1 antigen was used) and 86.4% of these were reactive to BuHV-1 only, whereas 11.8% showed absorbance values for both antigens and were classified as inconclusive. There was a statistically significant age-related difference in BuHV-1 infection rates but not in overall individual (47% vs. 58%) or herd prevalence (100% vs. 90%) of infection between the two regions.

Conclusion: The low percentage of sera reactive to BoHV-1 (1.8%, 12/643) indicates that BuHV-1 may be the main circulating alphaherpesvirus infection in Mediterranean water buffalo in the two study areas. Since Bubalus bubalis is included in Directive 64/432/EEC on animal health problems affecting intra-community trade in bovine animals, diagnostic testing with nonspecific ELISA for BoHV-1 infection in buffalo may yield false-positive reactions. This scenario could lead to economic losses and hamper buffalo trade and movement, particularly for reproduction purposes.     

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 ± 0.72 µg/ml, which declined to 0.22 ± 0.01 µg/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 ± 0.46/h), and by the drug''s rate of transfer constant from the central to the peripheral compartment, K₁₂ (4.94 ± 0.31/h). The elimination halflife and the volume of distribution were 2.14 ± 0.02 h and 0.42 ± 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (Cl_B) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 ± 0.002 l/kg/h and 1.73 ± 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred.     

Isolation of new pregnancy-associated glycoproteins from water buffalo (Bubalus bubalis) placenta by Vicia villosa affinity chromatography

The present study describes the isolation and characterization of new pregnancy-associated glycoprotein molecules (PAG) from midpregnancy and late-pregnancy placentas in the water buffalo (Bubalus bubalis). After extraction, the homogenates are subjected to acid and ammonium sulfate precipitations followed by DEAE chromatography. Subsequently, the water buffalo PAG (wbPAG) from these solutions are enriched by Vicia villosa agarose (VVA) affinity chromatography. As determined by western blotting with anti-PAG sera, the apparent molecular masses of the immunoreactive bands from the VVA peaks range from 59.5 to 75.8 kDa and from 57.8 to 73.3 kDa in the midpregnancy and late-pregnancy placentas, respectively. Amino-terminal microsequencing of the immunoreactive proteins has allowed the identification of three distinct wbPAG sequences, which have been deposited in the SwissProt database: RGSXLTIHPLRNIRDFFYVG (acc. no. P85048), RGSXLTILPLRNIID (acc. no. P85049), and RGSXLTHLPLRNI (acc. no. P85050). Their comparison to previously identified proteins has shown that two of them are new because they have not been described before. Our results confirm the suitability of VVA chromatography for the enrichment of the multiple PAG molecules expressed in buffalo placenta.