Pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in adult goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose intravenous (i.v.) and intramuscular (i.m.) administrations of 2 mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography (HPLC) and the data collected were subjected to compartmental and noncompartmental kinetic analysis. This compound presented a relatively high volume of distribution (Vss=1.31 L/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.23 L/kg small middle doth, which is related to a long elimination half-life (t1/2beta=7.18 h and 6.70 h i.v. and i.m., respectively). Pharmacokinetic parameters were not significantly different between both routes of administration. Marbofloxacin was rapidly absorbed after i.m. administration (Tmax=0.9 h) and had high bioavailability (F=100.74%).     

Influence of Escherichia coli endotoxin-induced fever on the pharmacokinetic behavior of marbofloxacin after intravenous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (Vss = 0.72 +/- 0.15 L/kg) lower than normal goats (Vss = 1.19 +/- 0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl) decreased from 0.24 +/- 0.12 L/kg/h in healthy animals to 0.13 +/- 0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC). Consequently, mean residence time (MRT) was also slightly increased in sick animals (MRT = 5.28 +/- 00.99 and 6.09 +/- 01.45 h, in healthy and febrile animals, respectively).     

Antibacterial efficacy and pharmacokinetic studies of ciprofloxacin on Pasteurella multocida infected rabbits

Twenty four isolates of Pasteurella multocida were taken from 74 diseased rabbits which suffered from respiratory manifestations with an incidence 35.1%. All isolated strains were identified biochemically and serologically as Pasteurella multocida type 3. The in vitro sensitivity test proved that Ciprofloxacin was the most effective antibiotic which was used for treatment of diseased rabbits. There was no isolation of Pasteurella multocida organism from all treated rabbits with Ciprofloxacin which can eliminate the causative organism, and control the infection within the examined rabbit colony. The kinetics of Ciprofloxacin, a fluoroquinolone, was studied after multiple oral and I/V dose of 20 mg/kg b. wt. In healthy rabbits and in those diseased with Pasteurella multocida Ciprofloxacin was given at a dose (20 mg kg-1/day) orally for successive 5 days. Serum levels reached their peak Tmax, at 2.321 and 2.524 hrs. in healthy and infected rabbits after oral administration, with absorption half-life (t0.5 (ab)) of 1.22 and 2.41 hrs. and elimination half-life (t0.5 (B)) of 2.24 and 1.28 hour respectively. Following I/V injection the kinetics of Ciprofloxacin follow two compartment model with (t0.5 (B)) 1.201 and 0.82 hour for normal and infected rabbits, (Vd (area)) of 0.653 and 0.563 L/kg and total body clearance CL(B) of 0.385 and 0.358 L/kg/hr respectively. High tissue concentrations of the drug were recorded in the kidneys, lung, spleen, liver, and muscle of diseased rabbits, while in healthy animal group the highest concentrations were achieved in kidney, liver, lung, spleen, and muscle. The high Ciprofloxacin tissue concentrations indicate that the Ciprofloxacin may be an excellent drug for treating urinary and respiratory tract infections.     

Polypeptides associated with Pasteurella multocida infection in rabbits.

Polypeptides from whole cell preparations of Pasteurella multocida serotypes A:12 and A:3 were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose paper. Antigens were detected by immunoblot analysis, using sera from 3 groups of rabbits. Sera were obtained from rabbits inoculated intranasally with P multocida serotype A:12 or A:3, from rabbits maintained in a rabbitry with enzootic P multocida A:12 infection, and from rabbits maintained in a rabbitry with enzootic P multocida A:3 infection. Immunoblot analyses of pre- and postinoculation sera from experimentally infected rabbits, using serotype A:12 antigen, revealed 3 polypeptides with approximate molecular mass of 28, 30, and 37 kDa that consistently detected antibodies after P multocida-induced infection. Sera from rabbits naturally infected with either serotype, tested against serotype A:12 and A:3 antigens, detected the same polypeptides in both serotypes. Thus, immunologic reactivity to these polypeptides may be useful for serologic detection of P multocida infection.     

Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration to ostriches

The pharmacokinetics of marbofloxacin was investigated after intravenous (IV) and intramuscular (IM) administration, both at a dose rate of 5 mg/kg BW, in six clinically healthy domestic ostriches. Plasma concentrations of marbofloxacin was determined by a HPLC/UV method. The high volume of distribution (3.22+/-0.98 L/kg) suggests good tissue penetration. Marbofloxacin presented a high clearance value (2.19+/-0.27 L/kgh), explaining the low AUC values (2.32+/-0.30 microgh/mL and 2.25+/-0.70 microgh/mL, after IV and IM administration, respectively) and a short half life and mean residence time (t(1/2 beta)=1.47+/-0.31 h and 1.96+/-0.35 h; MRT=1.46+/-0.02 h and 2.11+/-0.30 h, IV and IM, respectively). The absorption of marbofloxacin after IM administration was rapid and complete (C(max)=1.13+/-0.29 microg/mL; T(max)=0.36+/-0.071 h; MAT=0.66+/-0.22 h and F (%)=95.03+/-16.89).     

Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration

The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.     

Naturally acquired Pasteurella multocida infection in rabbits: clinicopathological aspects.

A cohort of 41 New Zealand White rabbits, 35 to 60 days old, from twelve litters were followed for twelve weeks for development of pasteurellosis. Eleven of 19 rabbits in five litters acquired Pasteurella multocida infection. The incubation period was difficult to determine as P. multocida infection was detected both before and after the onset of rhinitis. The response of rabbits to infection varied from subclinical infection to death from systemic pasteurellosis. Atrophy of the maxilloturbinates of the nares was detected in rabbits with chronic rhinitis associated with P. multocida infection.     

Pharmacokinetics of clindamycin phosphate in dogs after single intravenous and intramuscular administrations.

Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes. The disposition curve for IV administration was best represented as a 2-compartment open model. Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration. Bioavailability after IM administration was 87%. Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval. Intramuscular administration induced signs of pain and cannot be recommended.     

Comparative Pharmacokinetics and bioavailability of marbofloxacin in geese (Anser Anser domesticus) after two sites of intramuscular administrations

The pharmacokinetics of marbofloxacin (MAR) was compared in geese (Anser Anser domesticus) after single intravenous (IV) and intramuscular (IM) (thigh and pectoral muscles) administrations of 5 mg/kg. Serum concentrations of MAR were determined with high-performance liquid chromatography (HPLC) method. Serum MAR concentrations versus time were analyzed by a noncompartmental method. After IV administration, MAR showed high volume of distribution at steady state (V_dss) of 5.24 ± 1.08 L/kg. The serum body clearance (Cl) and elimination half-life (T_1/2λz) of MAR were 0.79 ± 0.07 L hr⁻¹ kg⁻¹ and 6.94 ± 1.12 hr, respectively. The peak of MAR serum concentrations C_max achieved at one and 0.50 hr after thigh and pectoral IM sites of injections, respectively, were 1.20 and 0.91 μg/ml. Significant differences were found in the mean absorption time (MAT), the systemic bioavailability (F%), and elimination parameters of MAR between two sites of injections, indicating that the absorption was fairly slow and complete after thigh IM injection. The pharmacokinetics of MAR in geese diverged according to the site of IM injection following a parallel study design. We recommend the thigh muscle as IM site of injection to obtain maximum concentrations of the administered drug in geese.     

The pathology of experimental respiratory infection with Pasteurella multocida and Bordetella bronchiseptica in rabbits

Groups of female New Zealand White rabbits, 8-10 weeks old, were inoculated intranasally with three different Pasteurella multocida serotypes (A:3, A:4 and A:12) or one of three Bordetella bronchiseptica strains of rabbit origin. Seven out of 18 rabbits died of experimental infection with P. multocida. B. bronchiseptica killed 3 out of the 8 animals inoculated with it. Deaths occurred between 3 and 6 days postinoculation (PI). In the rabbits that died of P. multocida inoculation, necropsy and histology revealed severe pleuritis with the accumulation of a remarkable amount of fibrinopurulent exudate in the thoracic cavity, serous rhinitis and tracheitis, acute hepatitis with necrotic foci in the parenchyma, and atrophy of the lymphoid organs and tissues. Rabbits killed 10 days PI developed only subacute serous rhinitis and hyperplasia of the lymphoid tissues. Rabbits that died of B. bronchiseptica inoculation showed acute serous rhinitis, acute catarrhal-fibrinopurulent pneumonia and mild pleuritis. As opposed to P. multocida inoculated animals, hepatitis and atrophy of the lymphoid tissues were not characteristic of these rabbits. Rabbits killed 10 days PI developed subacute purulent and necrotic pneumonia with remarkable macrophage proliferation, involving all lobes, and hyperplasia of the lymphoid tissues.     

Pharmacokinetics of marbofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration

To evaluate the fate and disposition of marbofloxacin (MBF) in freshwater crocodiles (Crocodylus siamensis), MBF was administered either intravenously (i.v.) or intramuscularly (i.m.) at a dosage of 2.0 mg/kg body weight. The concentrations of MBF in plasma were measured using high‐performance liquid chromatography equipped with a fluorescence detector. The concentrations of MBF in the plasma were measurable up to 144 h after i.v. and i.m. administration. After the first 45 min, the mean pharmacokinetic profiles produced by the two administration routes were almost identical. No statistically significant differences in the pharmacokinetic parameters between the groups were observed. The half‐life was long (about 2.5 days), the volume of distribution was large (about 1.44 L/kg), λz was small (0.01 h^?1), and the clearance was slow (22.6 mL/h/kg). The absolute i.m. bioavailability (F%) was 105.36%. The dose of MBF administered in this study seems to produce appropriate PK‐PD parameters that predict antibacterial success for disease caused by susceptible bacteria. More studies are warranted to evaluate the likely residues after administration of multiple doses.     

Pharmacokinetic behavior and pharmacokinetic/pharmacodynamic integration of marbofloxacin after subcutaneous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.     

Identification of Pasteurella multocida Serogroup F isolates in rabbits

A total of 24 Pasteurella multocida rabbit isolates obtained from 24 rabbit flocks in the Czech Republic during the period of between 2001 and 2004 were analysed by capsular PCR typing. Apart from isolates identified as serogroups A (n = 14, 58.4%) and D (n = 2, 8.3%), eight isolates (33.3%) were identified as members of serogroup F. This serogroup had been predominantly associated with poultry infections so far. The rabbit serogroup F isolates were characterized in detail by ribotyping with restriction to endonuclease MspI revealing two distinct ribotypes. Seven serogroup F isolates were assigned to ribotype 1 and one isolate was assigned to ribotype 2.     

麝鼠巴氏杆菌分离鉴定及其对组织病理性损伤

巴氏杆菌病由多杀性巴氏杆菌所引起的家畜、野禽和野生动物共患的一种以败血症和出血性炎症为特征的急性传染病,其发病率和死亡率很高,严重危害动物养殖业.     

Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and pharmacodynamic integration and modelling of marbofloxacin in calves for Mannheimia haemolytica and Pasteurella multocida

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin were established in calves for six strains of each of the pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. The distribution of marbofloxacin into inflamed (exudate) and non-inflamed (transudate) tissue cage fluids allowed comparison with the serum concentration–time profile. To establish the PD profile, minimum inhibitory concentration (MIC) was determined in Mueller–Hinton broth (MHB) and calf serum.Moderately higher MICs were obtained for serum compared to MHB. An initial integration of PK–PD data established C_max/MIC ratios of 45.0 and AUC_24h/MIC values of 174.7 h, based on serum MICs, for both bacterial species. Using bacterial time-kill curves, generated ex vivo for serum marbofloxacin concentrations, PK–PD modelling established three levels of growth inhibition: AUC_24h/MIC ratios for no reduction, 3 log₁₀ and 4 log₁₀ reductions in bacterial count from the initial inoculum count were 41.9, 59.5 and 68.0 h for M. haemolytica and 48.6, 64.9 and 74.8 h for P. multocida, on average respectively. Inter-strain variability for 3 log₁₀ and 4 log₁₀ reductions in bacterial count was smaller for P. multocida than for M. haemolytica. In conjunction with literature data on MIC₉₀ values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular injection in rabbits.

The pharmacokinetics and bioavailability of enrofloxacin were determined after IV and IM administration of 5 mg/kg of body weight to 6 healthy adult rabbits. Using nonlinear least-squares regression methods, data obtained were best described by a 2-compartment open model. After IV administration, a rapid distribution phase was followed by a slower elimination phase, with a half-life of 131.5 +/- 17.6 minutes. The mean body clearance rate was 22.8 +/- 6.8 ml/min/kg, and the mean volume of distribution was 3.4 +/- 0.9 L/kg. This large volume of distribution and the K12/K21 ratio close to 1, indicated that enrofloxacin was widely distributed in the body, but not retained in tissues. After a brief lag period (6.2 +/- 2.86 min), IM absorption was rapid (4.1 +/- 1.3 min) and almost complete. The mean extent of IM absorption was 92 +/- 11%, and maximal plasma concentration of 3.04 +/- 0.34 micrograms/ml was detected approximately 10 minutes after administration.