Haritova A M, Rusenova N V, Parvanov P R, Lashev L D, Fink-Gremmels J
Department of Pharmacology, Physiology and Chemistry, Trakia University, Bulgaria.
Vet Res Commun. 2006 Oct;30(7):775-89. doi: 10.1007/s11259-006-3400-7.
Colibacillosis is a systemic disease responsible for important economic losses in poultry breeding; fluoroquinolones, including danofloxacin, are used to treat diseased animals. The purpose of the present study was to estimate pharmacokinetic-pharmacodynamic (PK-PD) surrogates for bacteriostasis, bactericidal activity and bacterial elimination against Escherichia coli O78/K80, using a PK-PD approach, for danofloxacin in turkeys after oral administration. Eight healthy turkeys, breed BUT 9, were included in a two-way crossover study. The drug was administered intravenously (i.v.) and orally at a dose rate of 6 mg/kg bw. The values of the elimination half-life and the total body clearance after i.v. administration were 8.64 +/- 2.35 h and 586.76 +/- 136.67 ml kg(-1)h(-1), respectively. After oral administration, the values of the absolute bioavailability and the elimination half-life were 78.37+/- 17.35% and 9.74+/- 2.93 h, respectively. The minimum inhibitory concentration against the investigated strain in turkey serum was 0.25 microg/ml, four times higher than in broth. The lowest effective ex vivo AUC(24)/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coli O78/K80 were 0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the present study could be interpreted as being sufficient to eliminate E. coli with an MIC 0.25 microg/ml. However, considering the demand that antimicrobial resistance should be avoided by complete bacterial elimination, PK-PD considerations suggest that an even higher dose of 32 mg/kg per day or 0.7 mg/kcal per day should be evaluated in clinical trials.
大肠杆菌病是一种全身性疾病，在家禽养殖中会造成重大经济损失；氟喹诺酮类药物，包括达氟沙星，被用于治疗患病动物。本研究的目的是采用药代动力学-药效学（PK-PD）方法，评估口服给药后达氟沙星对火鸡体内大肠杆菌O78/K80的抑菌、杀菌活性及细菌清除的PK-PD替代指标。八只健康的BUT 9品种火鸡被纳入一项双向交叉研究。药物以6 mg/kg体重的剂量静脉注射（i.v.）和口服给药。静脉注射给药后的消除半衰期和全身清除率值分别为8.64±2.35小时和586.76±136.67 ml kg⁻¹ h⁻¹。口服给药后，绝对生物利用度和消除半衰期值分别为78.37±17.35%和9.74±2.93小时。火鸡血清中对所研究菌株的最低抑菌浓度为0.25μg/ml，比肉汤中的高四倍。对大肠杆菌O78/K80进行抑菌、杀菌活性和完全杀灭所需的最低有效体外AUC(24)/MIC比值分别为0.416小时、1.9小时和6.73小时。本研究中使用的6 mg/kg口服剂量可被认为足以清除MIC为0.25μg/ml的大肠杆菌。然而，考虑到应通过完全清除细菌来避免抗菌药物耐药性的要求，PK-PD考量表明在临床试验中应评估更高剂量，即每天32 mg/kg或每天0.7 mg/kcal。
