The Disposition Kinetics,Urinary Excretion and Dosage Regimen of Ciprofloxacin in Buffalo Calves (Bubalus bubalis)

The disposition kinetics, urinary excretion and a dosage regimen for ciprofloxacin after a single intravenous administration of 5 mg/kg was investigated in 5 healthy buffalo calves. The disposition kinetics were best fitted to a three-compartment open model. After 1 min, the concentration of ciprofloxacin in plasma was 8.50±0.39 g/ml and the minimum therapeutic concentration was maintained for 10 h. The elimination half-life and volume of distribution were 3.88 and 0.08 h and 3.97±0.22 L/kg, respectively. The total body clearance and T/P ratio were 0.709±0.025 L/kg per h and 6.13±0.54, respectively. Approximately 28.3% of the total administered dose of ciprofloxacin was recovered in urine within 24 h of administration. To maintain a minimum therapeutic plasma concentration of 0.10 g/ml, a satisfactory intravenous dosage regimen of ciprofloxacin, computed on the basis of disposition kinetic data obtained in healthy buffalo calves, would be 3 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     

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.     

Disposition and dosage regimen of cephaloridine in calves

The disposition and dosage regimen of cephaloridine were investigated in healthy calves following a single intramuscular administration of 10 mg/kg. The absorption halflife, climination halflife, apparent volume of distribution and total body clearance were 0.107±0.025 h, 2.08±0.14 h, 0.70±0.07L kg^-1 and 235.8±21.9 ml kg^-1 h^-1, respectively. Therapeutic plasma levels (1 g/ml) were maintained for up to 7 h. A satisfactory intramuscular dosage regimen for cephaloridine in calves would be 10 mg/kg repeated at 8 h intervals.     

The pharmacokinetics of primaquine in calves after subcutaneous and intravenous administration

The pharmacokinetics of primaquine was studied in calves of 180–300 kg live weight. Primaquine was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously (IV) or subcutaneously (SC) and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high-performance liquid chromatography. The extrapolated concentration of primaquine at zero time after IV administration was 0.50±0.48 µg/ml (mean ±SD) which decreased with an elimination half-life of 0.16±0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.50±0.08 µg/ml at 1.67±0.15 h after IV administration. The corresponding value was 0.47±0.07 µg/ml at 5.05±1.20 h after SC administration. The elimination half-lives of carboxyprimaquine after IV and SC administration were 15.06±0.99 and 12.26±3.06 h, respectively. The areas under the concentration-time curve for carboxyprimaquine were similar following either IV or SC administration of primaquine; the values were 11.85±2.62 µg.h/ml after the former and 10.95±2.65 µg.h/ml after the latter. The mean area under the concentration-time curve for primaquine was less than 0.1 µg.h/ml after either route of administration.Abbreviations AUC area under the concentration-time curve - CPRQ carboxyprimaquine - IV intravenous - 6M8AQ 6-methoxy-8-aminoquinoline - PRQ primaquine - SC subcutaneous     

Pharmacokinetics and Dosage Regimen of Ceftriaxone in Buffalo Calves

The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.     

Disposition Kinetics and Urinary Excretion of Pefloxacin after Intravenous Injection in Crossbred Calves

The disposition kinetics and urinary excretion of pefloxacin after a single intravenous administration of 5 mg/kg were investigated in crossbred calves and an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of pefloxacin in the plasma was 18.95±0.892 g/ml, which declined to 0.13±0.02 g/ml at 10 h. The pefloxacin was rapidly distributed from the blood to the tissue compartment as shown by the high values for the initial distribution coefficient, (12.1±1.21 h^–1) and the constant for the rate of transfer of drug from the central to the peripheral compartment, K ₁₂ (8.49±0.99 h^–1). The elimination half-life and volume of distribution were 2.21±0.111 h and 1.44±0.084 L/kg, respectively. The total body clearance (Cl_B) and the ratio of the drug present in the peripheral to that in the central compartment (P/C ratio) were 0.454±0.026 L/kg h) and 5.52±0.519, respectively. On the basis of the pharmacokinetic parameters obtained in the present study, an appropriate intravenous dosage regimen for pefloxacin in cattle for most of the bacteria sensitive to it would be 6.4 mg/kg repeated at 12 h intervals.     

Pharmacokinetics and Dosage Regimen of Enrofloxacin in Buffalo Bulls after Intramuscular Administration

The disposition kinetics and dosage regimen of enrofloxacin were investigated in breeding buffalo bulls following a single intramuscular administration of 5 mg/kg. The absorption half-life, half-life of the terminal phase, apparent volume of distribution and total body clearance were 0.262±0.099 h, 1.97±0.23 h, 0.61±0.13 L/kg and 210.2±18.6 ml/(kg.h), respectively. Therapeutic plasma levels (1 g/ml) were maintained for up to 6 h. A satisfactory intramuscular dosage regimen for enrofloxacin in buffalo bulls would be 8.5 mg/kg followed by 8.0 mg/kg at 8 h intervals.     

Intramuscular Kinetics and Dosage Regimens for Pralidoxime in Buffalo Calves (Bubalus bubalis)

The plasma levels, disposition kinetics and a dosage regimen for pralidoxime (2-PAM) were investigated in male buffalo calves following single intramuscular administration (15 or 30 mg/kg). The effects of 2-PAM on various blood enzymes were also determined. The absorption half-life, elimination half-life, apparent volume of distribution and total body clearance of 2-PAM were 1.08±0.19 h, 3.14–3.19 h, 0.83–1.01 L/kg and 184.9–252.1 ml/(kg h), respectively. At doses of 15 and 30 mg/kg body weight, a plasma concentration 4 g/ml was maintained for up to 4 and 6 h, respectively. Pralidoxime significantly lowered the serum level of transferases, phosphatases and lactate dehydrogenase but did not influence the acetylcholinesterase and carboxylesterase enzymes. The most appropriate dosage regimen for 2-PAM in the treatment of organophosphate toxicity in buffaloes would be 25 mg/kg followed by 22 mg/kg at 8 h intervals.     

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     

Influence of <Emphasis Type="Italic">E. coli</Emphasis> lipopolysaccharide induced fever on the plasma kinetics of cefepime in cross-bred calves

The pharmacokinetic behavior of cefepime was studied in healthy and febrile cross-bred calves after single intravenous administration (10 mg/kg). The fever was induced with E. coli lipopolysaccharide (1 μg/kg, IV). The drug concentration in plasma was detected by microbiological assay method using E. coli (MTCC 739) test organism. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by 2 compartment open model. At 1 min the concentration of cefepime in healthy and febrile animals were 55.3 ± 0.54 μg/ml and 50.0 ± 0.48 μg/ml, respectively and drug was detected up to 12 h. The elimination half-life of cefepime was increased from 1.26 ± 0.01 h in healthy animals to 1.62 ± 0.09 h in febrile animals. Drug distribution was altered by fever as febrile animals showed volume of distribution (0.27 ± 0.02 L/kg) higher than normal animal (0.19 ± 0.01 L/kg). Total body clearances in healthy and febrile animals were 104.4 ± 2.70 and 114.2 ± 1.20 ml/kg/h, respectively. To maintain minimum therapeutic concentration of 1 μg/ml, a satisfactory dosage regimen of cefepime in healthy and febrile cross-bred calves would be 15.5 mg/kg and 8.2 mg/kg body weight, respectively, to be repeated at 8 h intervals. The T>MIC values (8 h) of cefepime suggested that this agent is clinically effective in the treatment of various infections.     

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.     

Modification of the Pharmacokinetics and Dosage of Cefuroxime by Endotoxin-induced Fever in Buffalo Calves

The effect of endotoxin-induced fever on the pharmacokinetics and dosage regimen of cefuroxime was investigated in buffalo calves following a single intravenous dose of 10 mg/kg body weight. The fever was induced by intravenous administration of E. coli endotoxin at a dose of 1 g/kg body weight. The distribution and elimination half-lives were 0.100 h and 1.82 h, respectively, in healthy and 0.109 h and 2.28 h, respectively, in febrile buffalo calves. About 91% of the administered dose was excreted in the urine within 24 h. There was no effect of fever on the plasma protein binding of cefuroxime. The dosage regimen for intravenous administration of cefuroxime may be reduced in febrile conditions but the probability of this was only 0.3.     

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.     

Disposition kinetics and dosage regimen of levofloxacin on concomitant administration with paracetamol in crossbred calves

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 ± 0.36 µg/ml, which rapidly declined to 6.39 ± 0.16 µg/ml at 10 min. The drug level above the MIC₉₀ in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, α (17.3 ± 1.65 /h) and the ratio of K₁₂/K₂₁ (1.83 ± 0.12). The values of AUC and Vd_area were 12.7 ± 0.12 µg.h/ml and 0.63 ± 0.01 l/kg. The high ratio of the AUC/MIC (126.9 ± 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 ± 0.01 h, 1.88 ± 0.01 h and 0.32 ± 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

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.     

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.     

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     

Some Pharmacokinetic Parameters and Dosage Regimens for a Long-Acting Formulation of Oxytetracycline in 6- to 8-Month-Old Male Calves

A two-way crossover study was conducted in crossbred male calves (6–8 months old) to determine the bioavailability, pharmacokinetics and dosage regimens for a long-acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline after intravenous and intramuscular administration were 7.8 h and 24 h, respectively. The volume of distribution and total body clearance values of the drug were 0.86±0.07 L and 76.1±3.3 (ml/h)/kg, respectively. The maximum concentration of the drug in the serum (4.7–7.4 g/ml) was achieved 8–10 h after intramuscular administration. The minimum therapeutic serum concentration of drug of 0.5 g/ml was maintained between 15 min and 84 h after intramuscular administration. The intramuscular bioavailability of the drug was 89.1±4.2%. The dosage regimens to maintain the minimum therapeutic serum concentrations of OTC following intramuscular administration of OTC-LA were computed.