caa a22 4500 463238400 CHVBK 20180405153305.0 cr unu---uuuuu 170326e20070501xx s 000 0 eng 10.1007/s11259-006-3464-4 doi (NATIONALLICENCE)springer-10.1007/s11259-006-3464-4 Ismail M. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut Disposition Kinetics of Difloxacin After Intravenous, Intramuscular and Subcutaneous Administration in Calves [Elektronische Daten] [M. Ismail] The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration-time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t 1/2β) were 5.56 ± 0.33 h, 6.12 ± 0.42 h and 7.26 ± 0.6 h, respectively. The steady-state volume of distribution (V dss) was 1.12 ± 0.09 L/kg and total body clearance (ClB) was 2.19 ± 0.1 ml/(min. kg). The absorption half lives (t 1/2ab) were 0.38 ± 0.027 h and 2.1 ± 0.09 h, with systemic bioavailabilities (F) of 96.5% ± 6.4% and 84% ± 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C max) of 3.38 ± 0.13 μg/ml and 2.18 ± 0.12 μg/ml were attained after (t max) 1.22 ± 0.20 h and 3.7 ± 0.52 h. The MIC90 of difloxacin for Mannheimia haemolytica was 0.29 ± 0.04 μg/ml. The AUC/MIC90 and C max/MIC90 ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7-36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration. Springer Science + Business Media, Inc., 2007 difloxacin nationallicence Dicural nationallicence female calves nationallicence male calves nationallicence minimum inhibitory concentration nationallicence pharmacodynamics nationallicence pharmacokinetics nationallicence Mannheimia haemolytica nationallicence t 1/2α : distribution half-life nationallicence t 1/2β : elimination half-life (i.v.) nationallicence k 12 : first-order rate constant for transfer from central to peripheral compartment nationallicence k 21 : first-order rate constant for transfer from peripheral to central compartment nationallicence V c : apparent volume of the central compartment nationallicence V dss : volume of distribution at steady state nationallicence ClB : total body clearance nationallicence AUC0−∞ : area under curve from zero time to infinity nationallicence MRT : mean residence time nationallicence k ab : first-order absorption rate constant nationallicence t 1/2ab : absorption half-life nationallicence k el : first-order elimination rate constant nationallicence t 1/2el : elimination half-life (i.m. or s.c.) nationallicence MAT : mean absorption time nationallicence C max : maximum plasma concentration nationallicence t max : time to peak plasma concentration nationallicence F : systemic bioavailability nationallicence MIC90 : minimum inhibitory concentration nationallicence cfu : colony—forming unit nationallicence Veterinary Research Communications Kluwer Academic Publishers 31/4(2007-05-01), 467-476 0165-7380 31:4<467 2007 31 11259 https://doi.org/10.1007/s11259-006-3464-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11259-006-3464-4 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Ismail M. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut NATIONALLICENCE 773 0- Veterinary Research Communications Kluwer Academic Publishers 31/4(2007-05-01), 467-476 0165-7380 31:4<467 2007 31 11259 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer