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Marbofloxacin Disposition After Intravenous Administration of a Single Dose in Wild Mallard Ducks (Anas platyrhynchos)
Abstract
Marbofloxacin, a fluoroquinolone developed specifically for veterinary use, has demonstrated considerable pharmokinetic variation among avian species. The goal of this study was to determine the disposition kinetics of marbofloxacin in mallard ducks (Anas platyrhynchos) after a single intravenous injection. Six wild mallard ducks were used in the study. Marbofloxacin was injected at a dose of 2 mg/kg into the basilic vein, and blood was subsequently collected at regular intervals from each bird. Plasma marbofloxacin concentrations were determined by using high-performance liquid chromatography. The volume of distribution at steady state was 1.78 +/- 0.37 L/kg, and the total plasma clearance was 0.59 +/- 0.08 L/kg per hour. Marbofloxacin had a relatively short permanence, with a elimination half-life of 2.81 +/- 1.20 hours, a terminal half-life of 2.43 +/- 0.61 hours, and a mean residence time of 2.99 +/- 0.52 hour. The maximum observed concentration (Cmax) and area under the curve (AUC) were 1.34 +/- 0.27 microg/mL and 3.75 +/- 0.56 microg x h/mL, respectively. Values of minimum inhibitory concentration (MIC), Cmax, and AUC have been used to predict the clinical efficacy of a drug in treating bacterial infections, with a Cmax: MIC value of 10 and an AUC: MIC ratio of 125-250 associated with optimal bactericidal effects. By using the study data and MIC breakpoints of 0.125 microg/mL or 0.2 microg/mL, values derived for Cmax: MIC were 9.37 +/- 0.99 and 5.85 +/- 0.62, respectively, and for AUC: MIC were 29.99 +/- 4.51 and 18.74 +/- 2.82, respectively. By using MIC values of 0.125 and 0.2 microg/mL and a target AUC: MIC = 125, the calculated optimal daily marbofloxacin dosages for mallard ducks were 9.24 and 14.78 mg/kg, respectively. These results suggest that, primarily because of the high total plasma clearance observed, the marbofloxacin dose for treatment of bacterial diseases in mallard ducks should be increased after intravenous administration. Intravenous doses of 10-15 mg/kg should be assessed by studying their potential toxicity and efficacy in sick birds.
... 5 The pharmacokinetics of marbofloxacin have been investigated in a variety of avian species, most recently in ducks. [6][7][8] In Muscovy ducks (Cairina moschata), marbofloxacin had a good oral bioavailability (72% to 88%) and the recommended dosages from those studies were 2 to 2.5 mg/kg every 24 hours orally for the treatment of most Gram-negative bacteria (MIC o0.20 mg/mL). 7,8 In mallard ducks (Anas platyrhynchos), intravenous (IV) administration appeared to have high total plasma clearance, consequently a higher dosage of 10 to 15 mg/kg IV was recommended in that study. ...
... 7,8 In mallard ducks (Anas platyrhynchos), intravenous (IV) administration appeared to have high total plasma clearance, consequently a higher dosage of 10 to 15 mg/kg IV was recommended in that study. 6 Orbifloxacin Orbifloxacin is another fluoroquinolone with a similar antimicrobial spectrum as that of enrofloxacin and marbofloxacin. 9 Recently, pharmacokinetic and pharmacodynamic studies were completed in birds using Japanese quail (Coturnix japonica) as a model for small granivourous birds. ...
This article reviews advances in the pharmacokinetics and pharmacodynamics of therapeutic agents used in avian medicine. There has been a significant body of work published within the last 5 years that has helped provide a scientific basis for drug treatment in avian patients. This concise summary of different studies on antibacterial, antifungal, analgesic, sedative and anesthetic, hormone (e.g., deslorelin), psychotropic, antiepileptic, and cardiovascular drugs provides evidence of the advancements in this area of companion exotic animal medicine.
... Plasma concentration profiles showed a rapid initial distributive phase, followed by a slower elimination phase with an estimated mean distribution half-life (t 0.5α ) of 0.25 h. this result was longer than marbofloxacin (0.12 h) in chicken (Anadon et al., 2002) and shorter than marbofloxacin (1.58 h) in Mallard ducks(Garcia-Montijano et al., 2012). The elimination half-life (t 0.5β ) was 4.03 h. ...
In this study the disposition kinetics and plasma availability of marbofloxacin in Japanese quails after
single intravenous (IV), intramuscular (IM) and oral (PO) administrations of 5 mg/kg BW were investigated.
Following IV injection, elimination half-life (t1/2β), mean value of distribution at steady state (Vdss), total body
clearance (Cltot) and mean residence time (MRT) of marbofloxacin were 4.03 h, 1.24 l/kg, 0.19 l/h/kg and 5.89 h,
respectively. Following IM and PO administration of marbofloxacin at the same dose, the peak plasma concentration
(Cmax) were 3.86 and 3.59 μg/ml, respectively, which was obtained at 1.58 and 1.60 h, the time to peak concentration
(tmax) for both routes. Elimination half-lives (t1/2el) were 6.70 and 6.19 h, respectively, and mean absorption time
(MAT) was 1.79 and 1.19 h, respectively. The systemic bioavailability following IM and PO administration were
98.72 and 87.94%, respectively. In vitro protein binding percent was 26.38%. Analysis of pharmacokinetic data
obtained in this study reveals that a dosage of 5 mg/kg BW given by IM or PO routes every 24 h in Japanese quails
might be recommended for a successful clinical effect in quails.
Plasma disposition of orally administered enrofloxacin and marbofloxacin and their abilities to ensure appropriate plasma concentrations with respect to the minimal inhibitory concentrations of the targeted germs were compared in dogs (n=8). Oral doses of enrofloxacin and marbofloxacin were 5 and 2 mg.kg-1 respectively. As enrofloxacin has a main bacteriologically active metabolite (ciprofloxacin), the comparison was performed by measuring the plasma concentrations using validated specific HPLC and unspecific microbiological methods. It was shown that the plasma peak concentration was similar for both antibiotic but marbofloxacin was eliminated more slowly than enrofloxacin permitting effective plasma activities to he maintained for longer than enrofloxacin.
Fluoroquinolones are one of the most promising and vigorously pursued areas of contemporary antiinfective chemotherapy depicting broad spectrum and potent activity. They have a relatively simple molecular nucleus, which is amenable to many structural modifications. These agents have several favorable properties such as excellent bioavailability, good tissue penetrability and a relatively low incidence of adverse and toxic effects. They have been found effective in treatment of various infectious diseases. This paper is an attempt to review the therapeutic prospects of fluoroquinolone antibacterials with an updated account on their development and usage.
The rise in incidence of antimicrobial resistance, consumer demands and improved understanding of antimicrobial action has encouraged international agencies to review the use of antimicrobial drugs. More detailed understanding of relationships between the pharmacokinetics (PK) of antimicrobial drugs in target animal species and their action on target pathogens [pharmacodynamics (PD)] has led to greater sophistication in design of dosage schedules which improve the activity and reduce the selection pressure for resistance in antimicrobial therapy. This, in turn, may be informative in the pharmaceutical development of antimicrobial drugs and in their selection and clinical utility. PK/PD relationships between area under the concentration time curve from zero to 24 h (AUC(0-24)) and minimum inhibitory concentration (MIC), maximum plasma concentration (C(max)) and MIC and time during which plasma concentrations exceed the MIC have been particularly useful in optimizing efficacy and minimizing resistance. Antimicrobial drugs have been classified as concentration-dependent where increasing concentrations at the locus of infection improve bacterial kill, or time-dependent where exceeding the MIC for a prolonged percentage of the inter-dosing interval correlates with improved efficacy. For the latter group increasing the absolute concentration obtained above a threshold does not improve efficacy. The PK/PD relationship for each group of antimicrobial drugs is 'bug and drug' specific, although ratios of 125 for AUC(0-24):MIC and 10 for C(max):MIC have been recommended to achieve high efficacy for concentration-dependent antimicrobial drugs, and exceeding MIC by 1-5 multiples for between 40 and 100% of the inter-dosing interval is appropriate for most time-dependent agents. Fluoroquinolones, aminoglycosides and metronidazole are concentration-dependent and beta-lactams, macrolides, lincosamides and glycopeptides are time-dependent. For drugs of other classes there is limited and conflicting information on their classification. Resistance selection may be reduced for concentration-dependent antimicrobials by achieving an AUC(0-24):MIC ratio of greater than 100 or a C(max):MIC ratio of greater than 8. The relationships between time greater than MIC and resistance selection for time-dependent antimicrobials have not been well characterized.
To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws.
10 healthy blue and gold macaws.
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.
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.
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.
Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofloxacin has been licensed for use in various mammalian species, but not as yet for turkeys, although its kinetic properties distinguish it from other fluoroquinolones. For example, the longer half-life of marbofloxacin in many animal species has been appreciated in veterinary practice. It is generally accepted that, for fluoroquinolones, the optimal dose should be estimated on the basis of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the drug under consideration. Knowledge of these specific data for the target animal species allows the establishment of an integrated PK-PD model that is of high predictive value. In the present study, the antibacterial efficacy (PD indices) against a field isolate of Escherichia coli O78/K80 was investigated ex vivo following oral and intravenous administration of marbofloxacin to turkeys (breed BUT 9; six animals per group) at a dose of 2 mg/kg of body weight (BW). At the same time, the serum concentrations of marbofloxacin were measured at different time intervals by a standardized high-performance liquid chromatography method, allowing the calculation of the most relevant kinetic parameters (PK parameters). The in vitro serum inhibitory activity of marbofloxacin against the selected E. coli strain, O78/K80, was 0.5 mug/ml in the blood serum of turkeys, and the ratio of the maximum concentration of the drug in serum to the serum inhibitory activity was 1.34. The lowest ratio of the measured serum concentration multiplied by the incubation period of 24 h to the serum inhibitory activity required for bacterial elimination was lower than the ratio of the area under the serum concentration-time curve (AUC) to the serum inhibitory activity. These first results suggested that the recommended dose of 2 mg/kg BW of marbofloxacin is sufficient to achieve a therapeutic effect in diseased animals. However, considering the risk of resistance induction, the applied dose should be equal to an AUC/MIC of >125, the generally recommended dose for all fluoroquinolones. According to the PK-PD results presented here, a dose of 3.0 to 12.0 mg/kg BW per day would be needed to meet this criterion. In conclusion, the results of the present study provide the rationale for an optimal dose regimen for marbofloxacin in turkeys and hence should form the basis for dose selection in forthcoming clinical trials.
In this study the disposition kinetics and plasma availability of moxifloxacin in Muscovy ducks after single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of 5 mg kg−1 b.wt. were investigated. The concentrations of moxifloxacin in the plasma were measured using high-performance liquid chromatography (HPLC) with fluorescence detection on samples collected at frequent intervals after drug administration. Following intravenous injection, the decline in plasma drug concentration was bi-exponential with half-lives of (t1/2α) 0.22 ± 0.10 h and (t1/2β) 2.49 ± 0.26 h for distribution and elimination phases, respectively. The volume of distribution at steady-state (Vdss) was 1.02 ± 0.14 l kg−1 and the total body clearance (Cltot) was 0.32 ± 0.11 l kg−1 h−1, respectively. After intramuscular and oral administration of moxifloxacin at the same dose the peak plasma concentrations (Cmax) were 2.38 ± 0.43 and 2.11 ± 0.36 μg ml−1 and were obtained at 1.47 ± 0.26 and 1.83 ± 0.16 h (Tmax), respectively, the elimination half-lives (T1/2el) were 3.14 ± 0.42 and 2.63 ± 0.44 h, respectively, and AUC0–24 were 15.87 ± 2.35 and 14.52 ± 2.37 μg ml−1 h−1, respectively. The systemic bioavailabilities were 96.36 ± 11.54% and 86.79 ± 12.64%, respectively. In vitro plasma protein binding percent was 32%. We concluded that moxifloxacin might be clinically interesting alternative for the treatment of most sensitive bacterial infections in Muscovy ducks.
The pharmacokinetics properties of marbofloxacin were studied in adult Eurassian Griffon vulture after single-dose intravenous (IV) administration of 2mg/kg. Drug concentration in plasma was determined by high-performance liquid chromatography and the data obtained were subjected to compartmental and non-compartmental kinetic analysis. Marbofloxacin presented a volume of distribution at steady-state (Vdss) of 1.51±0.22L and total plasma clearance (Cl) of 0.109±0.023L/hkg. The permanence of this drug was long in vultures (T(1/2)(λ)=12.51±2.52h; MRT(∞)=13.54±2.29h). The optimal dose of marbofloxacin estimated is 2.73mg/kg per day for the treatment of infections in vultures with MIC(90)=0.2μg/mL.
1. The disposition kinetics and plasma availability of danofloxacin in Muscovy ducks after single intravenous (i.v.), intramuscular (i.m.) and oral administrations of 5 mg/kg body weight were investigated. 2. Tissue residue profiles (liver, kidney and muscle) and plasma were also studied after multiple intramuscular and oral administration of 5 mg/kg once daily for 5 consecutive days. 3. The concentrations of the drug in the plasma and tissues were measured using high-performance liquid chromatography (HPLC) with fluorescence detection on samples collected at frequent intervals after drug administration. 4. Following intravenous injection, plasma concentration vs. time curves were best described by a two compartment open model. The decline in plasma drug concentration was bi-exponential with half-lives of (t(1/2alpha)) 0.08 h and (t(1/2beta)) 3.91 h for distribution and elimination phases, respectively. 5. After intramuscular and oral administration of danofloxacin at the same dose the peak plasma concentrations (C(max)) were 0.89 and 0.81 microg/ml and attained at 1.17 and 1.21 h (T(max)), respectively, and the elimination half-lives (T(1/2el)) were 2.91 and 2.39 h, respectively. The systemic bioavailabilities were 103.21 and 89.26%, following i.m. and oral admisistartion, respectively. In vitro protein binding percent of danofloxacin in Muscovy ducks plasma was 17%. 6. The tissue level following i.m. and oral administration were highest in liver and kidney, respectively, and decreased in the following order: plasma and muscle. No danofloxacin residues were detected in tissues and plasma after 96 h with either route of administration except in liver and kidney, after 120 h in case of oral administration.
1. In this study the disposition kinetics and plasma availability of moxifloxacin in broiler chickens after single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of 5 mg/kg body weight were investigated. 2. Tissue residue profiles (liver, kidney, lung and muscle) and plasma were also studied after multiple intramuscular and oral administration of 5 mg/kg body weight, once daily for 5 consecutive days. 3. The concentrations of the drug in the plasma and tissues were measured using high-performance liquid chromatography (HPLC) with fluorescence detection on samples collected at frequent intervals after drug administration. 4. Following intravenous injection, plasma concentration-time curves were best described by a two-compartment open model. The decline in plasma drug concentration was bi-exponential with half-lives of (t(1/2alpha)) 0.26 h and (t(1/2beta)) 2.27 h for distribution and elimination phases, respectively. 5. After intramuscular and oral administration of moxifloxacin at the same dose the peak plasma concentrations (C(max)) were 2.23 and 1.99 microg/ml and were obtained at 1.56 and 1.90 h (T(max)), respectively, and the elimination half-lives (T(1/2el)) were 2.24 and 1.69 h, respectively. 6. The systemic bioavailabilities were 97.11 and 90.01%, respectively. In vitro protein binding percent was 37%. 7. The tissue levels following i.m. and p.o. administration were highest in liver and kidney, respectively, and decreased in the following order: plasma, lung and muscle. No moxifloxacin residues were detected in tissues and plasma after 120 h with both routes of administration, moxifloxacine was found in both the liver and kidney 144 h after i.m. and oral administration.
Six pregnant sows were treated in early pregnancy, late pregnancy and during lactation. Marbofloxacin was administered (2 mg/kg body weight) intravenously and orally. The active drug concentration in the plasma was quantitated by use of high performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated by use of statistical moments. In lactating animals, the concentrations in milk were also determined by HPLC. Mean elimination half-life of the drug after oral administration was significantly shorter in lactating sows (5.74h) than that of the early pregnancy group (10.09h). Total body clearance was highest in the lactating sows (3.27 ml/minute.kg body weight). The volume of distribution was large in all physiological states studied indicating good tissue penetration. Bioavailability was about 80% in pregnant and lactating sows. Antimicrobial secretion in milk contributed greatly to marbofloxacin elimination. These results indicate an important influence of lactation on marbofloxacin pharmacokinetics in sows. Therefore, in such cases, marbofloxacin dose should be increased during lactation.
The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chickens was investigated following single intravenous (i.v.) or oral administration (p.o.) and the steady-state plasma and tissue concentrations of both drugs were investigated after continuous administration via the drinking water. The following dosages approved for the treatment of chickens were used: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight. Concentrations of danofloxacin and enrofloxacin including its metabolite ciprofloxacin were determined in plasma and eight tissues by specific and sensitive high performance liquid chromatography methods. Pharmacokinetic parameter values for both application routes calculated by noncompartmental methods were similar for danofloxacin compared to enrofloxacin with respect to elimination half-life (t1/2: approximately 6-7 h), mean residence time (MRT; 6-9 h) and mean absorption time (MAT; 1.44 vs. 1.20 h). However, values were twofold higher for body clearance (ClB; 24 vs. 10 mL/min. kg) and volume of distribution at steady state (VdSS; 10 vs. 4 L/kg). Maximum plasma concentration (Cmax) after oral administration was 0.5 and 1.9 micrograms/mL for danofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drugs. Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxacin. Steady-state plasma concentrations (mean +/- SD) following administration via the drinking water were fourfold higher for enrofloxacin (0.52 +/- 0.16 microgram/mL) compared to danofloxacin (0.12 +/- 0.01 microgram/mL). The steady-state AUC0-24 h values of 12.48 and 2.88 micrograms.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area under the plasma concentration-time curve (AUC) values after single oral administration. For both drugs, tissue concentrations markedly exceeded plasma concentrations, e.g. in the target lung, tissue concentrations of 0.31 +/- 0.07 microgram/g for danofloxacin and 0.88 +/- 0.24 microgram/g for enrofloxacin were detected. Taking into account the similar in vitro activity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therapeutic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages.
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%).
Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration-time curve (AUC) and elimination half-life (t(1/2)el) values were 9.99 and 10.11 microg h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan-induced exudate, lipopolysaccharide-induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 microg h/mL after intravenous and 8.84, 8.53 and 8.52 microg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 microg/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 microg/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration-dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24-h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan-induced exudate and transudate) and 36 h (lipopolysaccharide-induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.
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.
To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens.
40 healthy broiler chickens.
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.
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.
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.
Information on the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in birds is scarce. Choice of drug and of dosage is usually empirical, since studies of anti-inflammatory drugs are lacking. In this study, three common veterinary non-steroidal anti-inflammatory drugs (NSAIDs) were administered intravenously to five different bird species. Sodium salicylate, flunixin and meloxicam were selected as anti-inflammatory drugs. These NSAIDs were administered intravenously to chickens (Gallus gallus), ostriches (Struthio camelus), ducks (Anas platyrhynchos), turkeys (Meleagris gallopavo) and pigeons (Columba livia). Plasma concentrations of the drugs were determined by validated high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. Most bird species exhibited rapid elimination of these drugs. Ostriches had the fastest elimination rate for all three NSAIDs, but there were some interesting species differences. Chickens had a half-life that was approximately 10-fold as long as the other bird species for flunixin. The half-life of chickens and pigeons was three-fold as long as the other bird species for meloxicam, and, for salicylic acid, the half-life in pigeons was at least three-five-fold longer than in the other bird species.
The fluoroquinolones are a class of compounds that comprise a large and expanding group of synthetic antimicrobial agents. Structurally, all fluoroquinolones contain a fluorine molecule at the 6-position of the basic quinolone nucleus. Despite the basic similarity in the core structure of these molecules, their physicochemical properties, pharmacokinetic characteristics and microbial activities can vary markedly across compounds. The first of the fluoroquinolones approved for use in animals, enrofloxacin, was approved in the late 1980s. Since then, five other fluoroquinolones have been marketed for use in animals in the United States, with others currently under investigation. This review focuses on the use of fluoroquinolones within veterinary medicine, providing an overview of the structure-activity relationship of the various members of the group, the clinical uses of fluoroquinolones in veterinary medicine, their pharmacokinetics and potential interspecies differences, an overview of the current understanding of the pharmacokinetic/pharmacodynamic relationships associated with fluoroquinolones, a summary of toxicities that have been associated with this class of compounds, their use in both in human and veterinary species, mechanisms associated with the development of microbial resistance to the fluoroquinolones, and a discussion of fluoroquinolone dose optimization. Although the review contains a large body of basic research information, it is intended that the contents of this review have relevance to both the research scientist and the veterinary medical practitioner.
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).
Chronic otitis externa in dogs is often associated with Pseudomonas aeruginosa infection. Fluoroquinolones are often used for treating such infections. Fluoroquinolone resistance mechanisms were characterized in 10 strains of P. aeruginosa isolated from chronic canine otitis externa. Nine out of ten strains harbored a mutation in the gyrA gene and presented an overexpression of efflux pump(s). There was a good correlation between the lipophilicity of the fluoroquinolone being tested and the effect of the efflux pump inhibitor in the final MIC. Therefore, both mechanisms, mutation in the gyrA gene and increased efflux pump(s), seem to play an important role in the acquisition of fluoroquinolone resistance in veterinary clinical isolates of P. aeruginosa. Levels of resistance to fluoroquinolones suggest that they could not be a good choice for systemic therapy of Pseudomonas otitis.
Bioavailability and pharmacokinetics of marbofloxacin in chickens
- X H Huang
- Z L Chen
- S T Zhang
- Z L Zeng
Huang XH, Chen ZL, Zhang ST, Zeng ZL.
Bioavailability and pharmacokinetics of marbofloxacin in chickens. J Chin Soc Vet Sci. 2002;
22(3):279-281.