Field evaluation of efficacy and tolerance of a 2% marbofloxacin injectable solution for the treatment of respiratory disease in fattening pigs

In a controlled and randomized field trial carried out in three European countries, 219 fattening pigs, from seven farms with respiratory disease problems, were treated intramuscularly for three or five days either with marbofloxacin 2 mg/kg/day, or with amoxicillin 7 mg/kg/day. Pigs were monitored daily until D5 (Day 5) and again at D21, and were weighed at D0 and D21. Pasteurella multocida, Actinobacillus pleuropneumoniae, and Mycoplasma hyopneumoniae were mainly identified in the pig lungs. The difference in the cure rate (74.5% in marbofloxacin group versus 68% in the amoxicillin group) was not significant. Mean rectal temperature was significantly lower after treatment with marbofloxacin. Other criteria tended to be favourable for the marbofloxacin group, although differences were not significant. The time to cure tended to be shorter for the marbofloxacin group (24.3% of pigs at 24 hours post-treatment versus 12.1% in the amoxicillin group). Marbofloxacin and amoxicillin relapse rates were 11.9% and 17.2% respectively (not significant) and daily weight gain was 746 g in the marbofloxacin group versus 687 g in the amoxicillin group (not significant). The 2% marbofloxacin solution was significantly better tolerated than amoxicillin.     

Efficacy of different treatment regimens of marbofloxacin in canine visceral leishmaniosis: a pilot study

This phase II, randomized, open-label field trial was designed to evaluate and compare the safety and efficacy of four treatment durations (10, 20, 28 or 40 days) with marbofloxacin administered orally at the dosage of 2mg/kg once a day for canine visceral leishmaniosis. Twenty-four dogs naturally infected with visceral leishmaniosis and without biochemical disorder evidences of renal insufficiency, were recruited by two Greek veterinarian clinics. They were also randomly assigned to one of the four treatment duration groups, and have been clinically, haematologically, biochemically and parasitologically followed-up regularly for 9 months. Efficacy was achieved for 5/6 dogs treated for 28 days, 4/6 dogs treated for 10 or 20 days and for 3/6 dogs treated for 40 days. Moreover, efficacy was reached more quickly (58.4 days) in dogs treated for 28 days. Improvement of clinical signs tended to be better and faster in the 28 days treatment group too. After 9 months of follow-up, a total of three cases could be considered as relapsing (two dogs treated for 40 days and one dog treated for 28 days). There was a significant reduction in amastigotes density in macrophages after 3 months in the four groups when compared with the parasite density at inclusion. No adverse effects were noticed during this 9 months study. Results obtained with marbofloxacin at the dosage of 2mg/kg once a day for 28 days seem encouraging and may offer a safe alternative for treating canine visceral leishmaniosis.     

Treatment of canine pyoderma with ibafloxacin and marbofloxacin--fluoroquinolones with different pharmacokinetic profiles

Dogs with superficial or deep pyoderma (n = 228) presented to first opinion veterinarians (n = 20) were treated orally with either ibafloxacin, at a dosage of 15 mg/kg, or marbofloxacin, at a dosage of 2 mg/kg, once daily for 3-16 weeks. On initial presentation, 35% of the cases were classified as having recurrent pyoderma and 40% as having deep pyoderma. Staphylococci (mainly Staphylococcus intermedius) were isolated from over 90% of the cases. The average treatment periods were 41 +/- 26 and 38 +/- 21 days in the ibafloxacin and marbofloxacin groups, respectively. One week after the cessation of treatment, 74 and 81% of dogs (P > 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having responded to treatment. One month after the cessation of treatment, 70% of the dogs in each group were still classified as cured or improved, and 3 and 11% (P < 0.05) in the ibafloxacin and marbofloxacin groups, respectively, were classified as having relapsed. Despite having different pharmacokinetic profiles, ibafloxacin and marbofloxacin produced similar results when used under field conditions at the recommended dosages.     

Absorption of enrofloxacin and marbofloxacin after oral and subcutaneous administration in diseased koalas (Phascolarctos cinereus)

Griffith, J.E., Higgins, D.P., Li, K.M., Krockenberger, M.B., Govendir, M. Absorption of enrofloxacin and marbofloxacin after oral and subcutaneous administration in diseased koalas (Phascolarctos cinereus). J. vet. Pharmacol. Therap. 33 , 595–604. Koalas (n = 43) were treated daily for up to 8 weeks with enrofloxacin: 10 mg/kg subcutaneously (s.c.), 5 mg/kg s.c., or 20 mg/kg per os (p.o.); or marbofloxacin: 1.0–3.3 mg/kg p.o., 10 mg/kg p.o. or 5 mg/kg s.c. Serial plasma drug concentrations were determined on day 1 and again at approximately 2 weeks, by liquid chromatography. The median (range) plasma maximum concentrations (C_max) for enrofloxacin 5 mg/kg s.c. and 10 mg/kg s.c. were 0.83 (0.68–1.52) and 2.08 (1.34–2.96) μg/mL and the median (range) T_max were 1.5 h (1–2) and 1 h (1–2) respectively. Plasma concentrations of orally dosed marbofloxacin were too low to be quantified. Oral administration of enrofloxacin suggested absorption rate limited disposition pharmacokinetics; the median (range) C_max for enrofloxacin 20 mg/kg p.o. was 0.94 (0.76–1.0) μg/mL and the median (range) T_max was 4 h (2–8). Oral absorption of both drugs was poor. Plasma protein binding for enrofloxacin was 55.4 ± 1.9% and marbofloxacin 49.5 ± 5.3%. Elevations in creatinine kinase activity were associated with drug injections. Enrofloxacin and marbofloxacin administered at these dosage and routes are unlikely to inhibit the growth of chlamydial pathogens in vivo.     

Plasma and tissue pharmacokinetics of marbofloxacin in experimentally infected chickens with Mycoplasma gallisepticum and Escherichia coli

The plasma and tissue pharmacokinetics of marbofloxacin in chickens experimentally infected with Mycoplasma gallisepticum and Escherichia coli were studied. Marbofloxacin was given to 66 infected chickens by oral administration at a dosage of 5 mg/kg b.w., once a day for three days. Plasma, brain, kidney, liver, lung, muscle and trachea were collected and marbofloxacin concentrations were analyzed by a high performance liquid chromatography method. In the infected chickens, maximal marbofloxacin concentrations in plasma, brain, kidney, liver, lung, muscle and trachea were 1.84, 1.33, 7.35, 5.61, 3.12, 2.98, and 4.51 g/mL (g); the elimination half‐lives of marbofloxacin were 6.8, 2.74, 9.31, 8.45, 9.55, 11.53 and 5.46 h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. AUC were calculated to be 9.68, 8.04, 45.1, 27.03, 20.56, 19.47, and 32.68 μg/mL (g) ·h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. Marbofloxacin concentration in tissues except for brain exceeded marbofloxacin concentration in plasma, with AUC_tissue/AUC_plasma ranging from 2.01 to 4.66 and Peak_tissue/Peak_plasma ranging from 1.62 to 3.99. The results showed that a marbofloxacin dosage of 5 mg/kg administered orally at 24 h intervals may provide successful treatment of chicken with MG and E. coli infection.     

Pharmacokinetics of marbofloxacin in horses

Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the terminal half-life 756 +/- 1.99 h. The marbofloxacin absolute bioavailabilities after subcutaneous and oral administration were 98 +/- 11% and 62 +/- 8%, respectively. The MIC required to inhibit 90% of isolates (MIC90) was 0.027 microg/ml for enterobacteriaceae and 0.21 microg/ml for Staphylococcus aureus. The values of surrogate markers of antimicrobial efficacy (AUIC, Cmax/MIC ratio, time above MIC90) were calculated and the marbofloxacin concentration profiles simulated for repeated administrations. These data were used to determine rational dosage regimens for target bacteria. Considering the breakpoint values of efficacy indices for fluoroquinolones, a marbofloxacin dosage regimen of 2 mg/kg bwt/24 h by i.v., subcutaneous or oral routes was more appropriate for enterobacteriaceae than for S. aureus.     

Therapy of difficult cases of canine pyoderma with marbofloxacin: a report of 39 dogs

Thirty-nine dogs with severe and/or recurrent lesions of pyoderma were treated with marbofloxacin at an average dosage of 2.12 mg/kg bodyweight, once daily, for time periods varing from 10 to 213 days. Forty-seven strains of bacteria, isolated from 34 cultures, were tested for sensitivity to various antibiotics. At day 0, no resistance to marbofloxacin was found, but one refractory case, a strain of Staphylococcus intermedius resistant to marbofloxacin, was cultured at day 28. Thirty-three dogs (84.6 per cent) showed an excellent response (cure), one (2.6 per cent) a clear improvement and one (2.6 per cent) a smaller improvement, while the remaining four dogs showed no response after 11 to 60 days. Fifteen dogs (45.5 per cent) relapsed over the follow-up period of three to 191 days, but none of the dogs in the study exhibited any adverse effects.     

Single-dose pharmacokinetics of marbofloxacin in Egyptian buffalo (Bubalus bubalis L.) steers

The objective of this study was to investigate the pharmacokinetics of marbofloxacin (MAR) following intravenous (iv) and intramuscular (im) administration of a 2.0 mg/kg body weight dosage to five healthy Egyptian buffalo steers. A cross-over design was used with a washout period of 2 weeks. Blood samples were obtained at 0, 5,10,15, and 20 min and at 0.5,0.75,1,2,4,6,8,10,12,24,30 and 48 hours after marbofloxacin administration.The serum marbofloxacin concentrations were quantitated using a modified agar diffusion bioassay method. Marbofloxacin exhibited a relatively high volume of distribution at steady-state (Vdss = 1.77 Lkg), which suggests good tissue penetration, and a total body clearance (Cltot) of 0.18 L/kgxh,which is associated with a long elimination half-life (tl/2beta = 7.52 h). Marbofloxacin was rapidly absorbed at a dosage of 2.0 mg/kg after im administration with an observed maximum serum concentration (Cmax) value of 2.004 microg/mL obtained at a time to peak concentration (tmax) of 0.5 h, and an absolute bioavailability (F %) of 86.79 +/- 5.53 %.The protein-binding ranged from 22 to 24.6 % with an average of 23.4 %. In conclusion, single iv and im administered doses of marbofloxacin were well tolerated by Egyptian buffalo steers. A dosage of 2 mg/kg body weight might not be enough to treat infections caused by bacteria with minimum inhibitory concentration (MIC) at or above 0.2 microg/mL, based on the calculated area under the inhibitory concentration (AUIC).     

Pharmacokinetic and pharmacodynamic testing of marbofloxacin administered as a single injection for the treatment of bovine respiratory disease

Vallé, M., Schneider, M., Galland, D., Giboin, H., Woehrlé, F. Pharmacokinetic and pharmacodynamic testing of marbofloxacin administered as a single injection for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap. 35, 519–528. New approaches in Pharmacokinetic/Pharmacodynamic (PK/PD) integration suggested that marbofloxacin, a fluoroquinolone already licensed for the treatment of bovine respiratory disease at a daily dosage of 2 mg/kg for 3–5 days, would be equally clinically effective at 10 mg/kg once (Forcyl^®), whilst also reducing the risk of resistance. This marbofloxacin dosage regimen was studied using mutant prevention concentration (MPC), PK simulation, PK/PD integration and an in vitro dynamic system. This system simulated the concentration–time profile of marbofloxacin in bovine plasma established in vivo after a single 10 mg/kg intramuscular dose and killing curves of field isolated Pasteurellaceae strains of high (minimum inhibitory concentration (MIC) MIC ≤0.03 μg/mL), average (MIC of 0.12–0.25 μg/mL) and low (MIC of 1 μg/mL) susceptibility to marbofloxacin. The marbofloxacin MPC values were 2‐ to 4‐fold the MIC values for all Mannheimia haemolytica, Pasteurella multocida tested. Marbofloxacin demonstrated a concentration‐dependant killing profile with bactericidal activity observed within 1 h for most strains. No resistance development (MIC ≥4 μg/mL) was detected in the dynamic tests. Target values for risk of resistance PK/PD surrogates (area under the curve (AUC) AUC_{24 h}/MPC and T_>MPC/T_MSW ratio) were achieved for all clinically susceptible pathogens. The new proposed dosing regimen was validated in vitro and by PK/PD integration confirming the single‐injection short‐acting antibiotic concept.     

Pharmacokinetic characteristics and tissue residues for marbofloxacin and its metabolite N-desmethyl-marbofloxacin in broiler chickens

OBJECTIVES: To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens. ANIMALS: 40 healthy broiler chickens. PROCEDURE: Two groups of chickens (groups A and B; 8 chickens/group) were administered a single IV and oral administration of marbofloxacin (2 mg/kg). Chickens of group C (n = 24) were given serial daily doses of marbofloxacin (2 mg/kg, PO, q 24 h for 3 days). Plasma (groups A and B) and tissue concentrations (group C) of marbofloxacin and its major metabolite N-desmethyl-marbofloxacin were determined by use of high-performance liquid chromatography. Residues of marbofloxacin and N-desmethylmarbofloxacin were measured in target tissues. RESULTS: Elimination half-life and mean residence time of marbofloxacin in plasma were 5.26 and 4.36 hours after IV administration and 8.69 and 8.55 hours after oral administration, respectively. Maximal plasma concentration was 1.05 microg/ml, and interval from oral administration until maximum concentration was 1.48 hours. Oral bioavailability of marbofloxacin was 56.82%. High concentrations of marbofloxacin and N-desmethyl-marbofloxacin were found in the kidneys, liver, muscles, and skin plus fat 24 hours after the final dose of marbofloxacin; however, marbofloxacin and N-desmethyl-marbofloxacin were detected in only hepatic (27.6 and 98.7 microg/kg, respectively) and renal (39.7 and 69.1 microg/kg, respectively) tissues 72 hours after termination of marbofloxacin treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of pharmacokinetic data obtained in this study reveals that a minimal therapeutic dose of 2 mg/kg, PO, every 24 hours should be appropriate for control of most infections in chickens.     

Use of a biological extract of Serratia marcescens to decrease doxorubicin-induced myelosuppression in dogs.

Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of marbofloxacin on Haemophilus parasuis nasal carriage

Haemophilus parasuis is a colonizer of the upper respiratory tract and the causative agent of Gl?sser's disease in swine. This study focused on the nasal carriage of H. parasuis after treatment with marbofloxacin. Three marbofloxacin treatments (three doses of 2mg/kg body weight [bw] every 24h, two doses of 4 mg/kg bw every 48 h and 8 mg/kg bw in one single shot) were used and all of them reduce significantly (p<0.05) the nasal carriage of H. parasuis as compared to control animals. Moreover, H. parasuis was not detected in the nasal cavities of piglets after administering the highest dose. The effect of a dose of 8 mg marbofloxacin/kg bw in one shot was further studied in a farm with clinical cases of Gl?sser's disease using a longitudinal study. Statistically significant reduction of nasal carriage of H. parasuis was detected during the first week after treatment in comparison with the control group. However, a clear relationship between the minimum inhibitory concentration (MIC) of the different strains, their putative virulence or the treatment group (antibiotic or control) from which they were isolated was not detected. Finally, the effect induced by the antibiotic treatment on the bacterial strains seemed to be transitory, since diverse H. parasuis strains (with high and low marbofloxacin MICs) were observed 7 days after finishing the treatment.     

Clinical efficacy of intravenous administration of marbofloxacin in a Staphylococcus aureus infection in tissue cages in ponies

Tissue cages (TC), implanted subcutaneously in the neck in eight ponies, were inoculated with Staphylococcus aureus (S. aureus) to determine the clinical efficacy of marbofloxacin in the treatment of this infection. From 21 h after inoculation, marbofloxacin (6 mg/kg) was administered intravenously (i.v.) once daily for 7 days. Samples of the tissue cage fluid (TCF) were taken to determine marbofloxacin concentrations (days 1, 3 and 7), using high-pressure liquid chromatography, and numbers of viable bacteria [colony forming units (CFU)] (days 1, 3, 7, 14 and 21). Statistical analysis was used to compare CFU before and after treatment. Clinical signs and CFU were used to evaluate the efficacy of treatment. Although, there was a slight decrease in CFU in all TC initially, the infection was not eliminated by marbofloxacin treatment in any of the ponies and abscesses formed. As the MIC (0.25 microg/mL) did not change during treatment and the concentration of marbofloxacin during treatment (mean concentration in TCF was 0.89 microg/mL on day 1, 0.80 microg/mL on day 3 and 2.77 microg/mL on day 7) was above MIC, we consider that the treatment failure might be attributable to the formation of a biofilm by S. aureus. Based on the present results, i.v. administration of marbofloxacin alone is not suitable for the elimination of S. aureus infections from secluded sites.     

Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs

OBJECTIVE: To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. ANIMALS: 12 adult mixed-breed and purebred hounds. PROCEDURE: 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. RESULTS: Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.     

Effect of experimental renal impairment on disposition of marbofloxacin and its metabolites in the dog

The pharmacokinetics of marbofloxacin was studied in eight healthy female Beagle dogs before and after moderate renal impairment was induced experimentally. A single intravenous (i.v.) administration and repeated administration for 8 days (2 mg/kg, once-a-day) of marbofloxacin were studied. Renal impairment was induced by a right kidney nephrectomy and electrocoagulation of the left kidney. An increase ( P  < 0.001) in the plasma concentrations of urea (from 3.8 ± 0.7 to 9.8 ± 2.1 mmol/L) and creatinine (from 78.8 ± 3.4 to 145.8 ± 22.3 μmol/L), and a significant decrease (2.9 ± 0.3 vs 1.5 ± 0.2 mL/kg/min) ( P  < 0.001) in glomerular filtration rate were observed in the renal-impaired dogs. The clearance of marbofloxacin was slightly decreased after the induction of renal failure (1.6 ± 0.2 to 1.4 ± 0.1 mL/kg/min) ( P  < 0.05), but no significant variation of volume of distribution at steady state ( V _ss) and mean residence time ( MRT ) was observed after intravenous administration of marbofloxacin ( P > 0.05). Following oral administration of marbofloxacin, an increase in total area under the concentration time curve ( AUC ) was observed after renal failure (from 10372 ± 1710 to 11459 ± 1119 mg.min/L) ( P  < 0.05), but indices of accumulation were not modified. An increase ( P  < 0.01) in the AUC of N-oxide-marbofloxacin was observed after surgery. In conclusion, renal impairment has no biologically relevant influence on marbofloxacin disposition and there is no need for dosage adjustment of marbofloxacin in dogs with mild renal impairment.     

Efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for the treatment of acute postpartum metritis in dairy cows

OBJECTIVE: To evaluate the efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for treatment of acute postpartum metritis (APM) in dairy cows. DESIGN: Multilocation, randomized block, field trial. ANIMALS: 406 cows in the first 14 days postpartum. PROCEDURE: Cows with rectal temperatures > or = 39.5 degrees C (103.1 degrees F) without clinical signs of respiratory or gastrointestinal tract disease and with a fetid vaginal discharge were allocated randomly in blocks of 3 to 3 treatment groups: sterile saline (0.9% NaCl) solution administered at a dosage of 2 mL/45.4 kg (2 mL/100 lb), SC or IM, once daily for 5 days (control); or ceftiofur hydrochloride administered at a dosage of 1.1 or 2.2 mg of ceftiofur equivalents (CE)/kg (0.5 or 1 mg/lb, respectively), SC or IM, once daily for 5 days. Cows were evaluated on days 6, 10, and 14, and clinical cure or failure to cure was determined. Clinical cure was defined as no additional antimicrobial treatment administered, rectal temperature < 39.5 degrees C, and absence of a fetid vaginal discharge. RESULTS: On day 14, clinical cure rates were 77%, 65%, and 62% for the 2.2 mg of CE/kg, 1.1 mg of CE/kg, and control groups, respectively. No significant differences were detected in clinical cure rates between control and treatment groups on day 10 or 6. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur hydrochloride administered at a dosage of 2.2 mg of CE/kg, SC or IM, once daily for 5 days was efficacious for treatment of APM in dairy cows.     

Efficacy of netobimin against Muellerius capillaris and resistant strain of digestive tract strongyles in dairy goats

The efficacy of netobimin against digestive tract strongyles and the small lungworm Muellerius capillaris was tested in a dairy goat herd. The drenches were given orally at the rate of 20 mg/kg of body weight once, 10 mg/kg on 2 successive days, or 7.5 mg/kg on 3 successive days. Fecal egg counts and larval counts were done 8 days before and on the day of drenching; further counts were performed on postdrenching days 8 and 18. Two goats were necropsied, 1 on postdrenching day 5 and 1 on day 10 in the group treated on 3 successive days. The fecal egg counts were reduced by 44 to 79% depending on dosage on postdrenching day 18; the remaining worms were Trichostrongylus colubriformis. The larval counts of M capillaris were reduced by 72 to 92%, depending on dose. The reduction was significant in all the treated groups, compared with that in the control group. The use of netobimin at the dosage of 10 mg/kg given on 2 successive days or 7.5 mg/kg given on 3 successive days might be recommended to treat goats infected with Muellerius spp and digestive tract strongyles.     

Pharmacokinetics of marbofloxacin in dogs after oral and parenteral administration

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h; Cl _B= 0.10 L/h.kg; V _area= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, C _max of 1.4 μg/mL was reached at t _max of 2.5 h. Mean AUC and C _max values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except t _max (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.     

A field comparison of the efficacy and tolerance of marbofloxacin in the treatment of bovine respiratory disease

A multicentre, controlled, randomized and blinded trial was carried out in 180 ruminating calves with pyrexia and respiratory sign(s) on nine Belgian, British and French farms. All animals were sampled for pathogenic bacteria before treatment and at failure/relapse. Calves were injected with either marbofloxacin (M) solution [Marbocyl (Laboratoire Vétoquinol, Lure, France) 10%] at 2 mg/kg/24 h for 4 days intravenously on the first day then subcutaneously, or tilmicosin (T) solution (Micotil, Elanco Products Ltd, Basingstoke, Hants, UK) at 10 mg/kg as a single subcutaneous (s.c.) injection. The animals were examined clinically eight times up to day 28. The bacterial pathogens were found to be sensitive to marbofloxacin: for Pasteurella haemolytica the minimum inhibitory concentration (MIC)90 was 0.08 microg/mL and for P. multocida the MIC90 was 0.04 microg/mL. Cure rates at day 4 for group M and group T were 84 vs. 82%, respectively (P > or = 0.05). However, overall clinical score was significantly lower after 1 day in group M (P < 0.05). There was no difference in either relapse rate or average daily weight gain between groups. Marbofloxacin was found to be better tolerated than tilmicosin at the s.c. injection site (77.5 vs. 42.2% calves without local swelling, P=0.001) and was well tolerated when injected intravenously. Marbofloxacin was shown to have comparable but faster efficacy and better local tolerance than tilmicosin in the treatment of bovine respiratory disease (BRD).     

Pharmacokinetics of marbofloxacin in blue and gold macaws (Ara ararauna)

OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. ANIMALS: 10 healthy blue and gold macaws. PROCEDURES: In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. RESULTS: After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microg.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microg/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microg.h/mL, and the harmonic mean terminal half-life was 4.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.