Clinical pharmacokinetics of parenterally administered danofloxacin in cattle

Giles, C. J.; Magonigle, R A; Grimshaw, W. T. R.; Tanner, A. C.; Risk, James; Lynch, Martin J.; Rice, John R.

doi:10.1111/j.1365-2885.1991.tb00854.x

Cited by 61 publications

(47 citation statements)

References 11 publications

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“…The pharmacokinetics of danofloxacin has been investigated in ruminant species including cattle (7,8,10), sheep (12), and goats (19). Following administration of danofloxacin, there is rapid distribution to the lungs (12) and high tissue concentrations are achieved in pneumonic lung, including areas of consolidation (1, 2).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical observations for signs of bovine respiratory disease and measurement of rectal temperature were carried out immediately prior to inoculation, immediately prior to treatment administration at time zero, and at 4,8,12,24,36, and 48 h thereafter. The respiratory rate, rectal temperature, character of respiration, and general demeanor were assessed for each calf.…”

Section: Methodsmentioning

confidence: 99%

“…Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (C max :MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Danofloxacin is a fluoroquinolone antimicrobial drug with rapid bactericidal activity against a broad range of pathogens responsible for a number of disease syndromes of economic importance in the commercial rearing of livestock (8,15). Since their introduction in the late 1980s, fluoroquinolones have been shown by a number of studies to exhibit concentration-dependent bactericidal activity, whereby the optimal effect is attained by the administration of high doses over a short period (4,6,14).…”

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Pharmacokinetic and Pharmacodynamic Profiles of Danofloxacin Administered by Two Dosing Regimens in Calves Infected withMannheimia(Pasteurella)haemolytica

Sarasola¹,

Lees

Aliabadi

et al. 2002

Antimicrob Agents Chemother

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The pharmacokinetics and pharmacodynamics of danofloxacin in calves with induced Mannheimia (Pasteurella) haemolytica pneumonia were evaluated. Calves received either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body weight) administered as either a single IV bolus or a 36-h continuous IV infusion. Blood samples and bronchial secretions were collected before and at predetermined times over 48 h following the start of treatment. Calves were assessed clinically throughout, and lung consolidation was assessed at necropsy. Bronchial secretions and lung tissue were cultured for M. haemolytica. Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (C max :MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Danofloxacin is a fluoroquinolone antimicrobial drug with rapid bactericidal activity against a broad range of pathogens responsible for a number of disease syndromes of economic importance in the commercial rearing of livestock (8,15). Since their introduction in the late 1980s, fluoroquinolones have been shown by a number of studies to exhibit concentration-dependent bactericidal activity, whereby the optimal effect is attained by the administration of high doses over a short period (4,6,14). This is a property shared by the aminoglycosides but is in contrast to the predominantly time-dependent bactericidal action shown by the ␤-lactam antibiotics (3), where the time that bacteria are exposed to antimicrobial concentrations exceeding the MIC (TϾMIC) is the major determinant of efficacy. These different types of action have been confirmed for danofloxacin and amoxicillin in an in vitro pharmacodynamic model against Actinobacillus pleuropneumoniae (9).The purpose of this study was to establish the pharmacokinetic and pharmacodynamic properties of danofloxacin in vivo by using an experimental model of calf pneumonia and to determine whether the concentration-dependent activity of danofloxacin in cattle operates under simulated clinical conditions. A fixed equal total dose of danofloxacin was administered either as a single intravenous (IV) bolus or by continuous infusion over a 36-h period, and the clinical and bacteriological outcomes in calves with induced infections of Mannheimia (Pasteurella) haemolytica were compared. The study was conducted in compliance with Good Clinical Practice guidelines (5), the analysis of samples was conducted in accordance with Good Laboratory Practice guidelines (16), and the husbandry of all animals was in compliance with the requirements of national legislation and local animal welfare guidelines. The study was conducted under veterinary supervision, with veterinary attention available at all times. MATERIALS AND METHODSAnimals. Thirty-three male Friesian calves (approximately 11 to 13 weeks of age, with initial body weights of 66.5 to 106 kg) were enrolled in the study and inoculated with M. haemolytica. Prior to enrollment, the calves were free from preexisting medic...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Pharmacokinetic and Pharmacodynamic Profiles of Danofloxacin Administered by Two Dosing Regimens in Calves Infected withMannheimia(Pasteurella)haemolytica

Sarasola¹,

Lees

Aliabadi

et al. 2002

Antimicrob Agents Chemother

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“…It achieves high concentrations in several tissues, including the lung (11,22,23,33). Moreover, studies in our laboratory have demonstrated that the volume of distribution exceeds 3 liters/kg in four ruminant species after intravenous (i.v.)…”

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Pharmacokinetics (PK), Pharmacodynamics (PD), and PK-PD Integration of Danofloxacin in Sheep Biological Fluids

Aliabadi

Landoni

Lees

2003

Antimicrob Agents Chemother

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The fluoroquinolone antimicrobial drug danofloxacin was administered to sheep intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1.25 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of danofloxacin in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) were established by using a tissue cage model. The in vitro and ex vivo activities of danofloxacin in serum, exudate, and transudate against a pathogenic strain of Mannheimia haemolytica were established. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 60.5, 85.6, and 45.7 h, respectively, after i.v. dosing and 55.9, 77.9, and 49.1 h, respectively, after i.m. dosing. After i.m. dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 10.8, 3.0, and 1.6, respectively. The ex vivo growth inhibition data after i.m. dosing were fitted to the inhibitory sigmoid E max equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.8, 20.2, and 28.7 h, and slightly higher values were obtained for transudate and exudate. It is proposed that use of these data might provide a novel approach to the rational design of dosage schedules.Danofloxacin is an antibacterial drug of the fluoroquinolone group developed for use in veterinary medicine. It achieves high concentrations in several tissues, including the lung (11,22,23,33). Moreover, studies in our laboratory have demonstrated that the volume of distribution exceeds 3 liters/kg in four ruminant species after intravenous (i.v.) dosing (28). However, only one previous publication has described the pharmacokinetics (PK) of danofloxacin in sheep (22).The spectrum of antimicrobial activity of danofloxacin is wide and includes most gram-negative bacteria and some gram-positive bacteria, mycoplasmas, and intracellular pathogens, such as Brucella and Chlamydia species; but it has poor activity against anaerobes (1,13,25,32). Detailed studies of its spectrum of activity against sheep pathogens have not been described, but MICs at which 90% of strains are inhibited (MIC 90 s) of Յ0.25 g/ml for the cattle pathogens Mannheimia haemolytica, Pasteurella multocida, Haemophilus somnus, Mycoplasma bovis, and Mycoplasma dispar have been reported (3,10,12,21).Bacterial diseases in sheep cause morbidity, mortality, suffering, and significant economic losses. Antibacterial drugs are therefore used in both treatment and prevention programs. However, there are only limited data on the pharmacology of antibacterial drugs in sheep. Such data are required for the design of rational dosage schedules for clinical use. In addition, the sheep is a suitable species for use in models of disease and inflammation because of its size, temperament, and the ease of repeated samplings of blood and other body fluids.The design of e...

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“…In fact they have been used successfully to treat infection caused by Gram positive and Gram negative bacteria. These compounds act by inhibiting the bacterial DNAgyrase (Gilles et al, 1991). Chemical structure of fluroquinolones when changed, an increase in the spectrum of activity and potency of the drugs is seen (Spoo et al, 1995).Enrofloxacin is one of the antibacterial agent which is widely used in veterinary medicine (Nouws et al, 1988).…”

Section: Introductionmentioning

confidence: 99%