Pharmacokinetics of enrofloxacin and marbofloxacin in Japanese quails and common pheasants

1. The pharmacokinetics of enrofloxacin and marbofloxacin was studied in Japanese quails and common pheasants. Healthy mature birds from both species and both genders were treated intravenously and orally with enrofloxacin (10 mg/kg) and marbofloxacin (5 mg/kg).

2. After intravenous administration enrofloxacin was extensively metabolised to ciprofloxacin. Metabolites of marbofloxacin were not detected. Values of volume of distribution were respectively 4.63 l/kg and 3.67 l/kg for enrofloxacin and 1.56 l/kg and 1.43 l/kg for marbofloxacin. In quails, total body clearance values were higher than those in pheasants and other avian species.

3. After oral application enrofloxacin was rapidly absorbed in quails, more rapidly than marbofloxacin. Pheasants absorbed both antimicrobials at a lower rate. Higher bioavailability was observed for marbofloxacin (118%). Relatively low bioavailability was established in quails for enrofloxacin (26.4%), accompanied by extensive conversion to ciprofloxacin.

4. Generally, quails absorbed and eliminated both fluoroquinolones more rapidly than pheasants; the latter showed pharmacokinetics similar to poultry. Because of favourable pharmacokinetic properties, marbofloxacin should be preferred for oral administration in Japanese quails and pheasants for treatment of infections caused by equally susceptible pathogens.

     

Impact of treated wastewater irrigation on water repellency of Mediterranean soils

Irrigation with treated wastewater (TWW) is gaining importance due to declining water availability in dry regions. TWW irrigation has various potential adverse effects on soil quality such as hydrophobic effects on soil surfaces, reducing initial sorptivity and promoting the formation of preferential flow paths. In May and June 2010, in situ infiltration measurements using mini disk tension infiltrometer were deployed in five different orchard plots in Israel to assess the impact of different irrigation water qualities on the soil water repellency index R. In most plantations, long-term test sites were accessed to compare adjacent plots irrigated with fresh water (FW) or TWW. Topsoil samples were analyzed for selected physical and chemical characteristics. The mean R values increased at all TWW sites, from +15 up to +55 % compared with FW sites. The water drop penetration time (WDPT) increased up to 30 fold at three of five TWW sites compared with FW sites. Subsequent U tests and multilevel analysis indicated an impact of the type of irrigation water on R and WDPT. Moreover, soil electrical conductivity and exchangeable sodium percentage were consistently higher at all TWW sites. These results show that irrigation water quality clearly influences physical and chemical properties of the soil.     

Pharmacokinetic-Pharmacodynamic Modelling of Danofloxacin in Turkeys

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^-1h^-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 μg/ml, four times higher than in broth. The lowest effective ex vivo AUC₂₄/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coliO78/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 μ g/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.     

Population Pharmacokinetics of Tobramycin in Horses

Population pharmacokinetics of tobramycin was investigated in 28 healthy horses, with an aim to assess interindividual variability in the disposition of the antibiotic. Additionally, a covariate model for improved prediction of the concentrations in a particular animal was developed. A two-compartmental model best described the data. The final population covariate regression model was based on relationships between body weight and central and peripheral volumes of distribution, and between creatinine clearance and systemic tobramycin clearance. The value of population systemic tobramycin clearance and its interindividual variation (CV) were 0.087 L.hr⁻¹.kg⁻¹ and 6.0%, respectively. The respective values for central and peripheral volumes of distribution were 0.652 L.kg⁻¹ with CV of 17.7% and 1.56 L.kg⁻¹ with CV of 4.5%. In horses with decreased glomerular filtration rate, lower tobramycin clearance is predicted with the population model that requires administration of lower dose than that accepted for treatment of horses with normal kidney function. Population pharmacokinetic analysis allows study of basic disposition of tobramycin in horses with sparse data. The prediction power of the regression model was improved by inclusion of covariables such as body weight and creatinine clearance. This model can be used in direct patient care for the construction of dosing strategy in individual clinical cases.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Male and Female Turkeys following Intravenous and Oral Administration

The pharmacokinetics of enrofloxacin (EFL) was investigated in turkeys (6 male and 6 female; 7-month-old at the start of the experiment), after intravenous and oral administration at a dose of 10 mg/kg body weight. The serum concentrations of EFL and its active metabolite ciprofloxacin (CFL) were determined by high-performance liquid chromatography. The serum concentrations vs time were analysed by a compartmental analysis. The mean values of EFL pharmacokinetic parameters showed differences only between values of V_d,ss (3.46±0.19 for the females and 4.53±0.11 L/kg for the males, p>0.05). The metabolite CFL was eliminated more slowly than its parent compound. There were no statistically significant differences between the values of the CFL pharmacokinetic parameters calculated for both sexes, excluding the higher values (p>0.05) of C_max in the females. The ratio AUC_CFL/AUC_EFL×100 was 4.4% in the male and 6.84% in the female birds. After oral administration of EFL the values of F(%) were 77.83 in the female and 79.61 in the male turkeys. Higher CFL serum concentrations were measured in females (p>0.05). The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in turkeys can be characterized as similar to that in chickens and very similar between both sexes.     

Pharmacokinetics of enrofloxacin in lactating sheep

The pharmacokinetics of enrofloxacin (ENR) was investigated after its intravenous (iv) and intramuscular (im) administration in six healthy lactating sheep. After iv ENR injection (as a bolus), the elimination half-life (t(1/2beta)), the volume of distribution (Vd(area)), and the area under the concentration vs. time curve (AUC) were 3.30 (0.36)h, 2.91 (0.17)l/kg and 4.19 (0.18) microg h/ml, respectively. The maximum milk concentrations of ENR (C(max)), the area under the milk concentration vs. time curve (AUC(milk)) and the ratio AUC(milk)/AUC(serum) were 2.38 (0.14)microg/ml, 23.76 (2.21) microg h/ml and 5.62 (0.30), respectively. After im administration of ENR the t(1/2beta), C(max), time of C(max) (t(max)) and absolute bioavailability (F(abs)) were 3.87 (0.10)h, 0.74 (0.07) microg/ml, 0.83 (0.12)h and 75.35%, respectively. The C(max), AUC(milk) and the ratio AUC(milk)/AUC(serum) were 1.94 (0.13) microg/ml, 24.81 (2.25) microg h/ml and 8.15 (0.96), respectively.     

Pharmacokinetics of Oleandomycin in Dogs After Intravenous or Oral Administration Alone and After Pretreatment With Metamizole or Dexamethasone

The pharmacokinetics of oleandomycin OLD) after intravenous and oral administration, both alone and after intramuscular pretreatment with metamizole or dexamethasone, were studied in healthy dogs. After intravenous injection of OLD alone 10 mg/kg as bolus), the elimination half-life t _1/2, volume of distribution V _{d, area}), body clearance CL_B) and area under the concentration-time curve AUC) were 1.60 h, 1.11 L/kg, 7.36 ml/kg)/min and 21.66 µg h/ml, respectively. There were no statistically significant differences following pretreatment with metamizole or dexamethasone. After oral administration of OLD alone, the t _frac12;, maximum plasma concentrations C _max), time of C _max t _max), mean absorption time MAT) and absolute bioavailability F _abs) were 1.68 h, 5.34 µg/ml, 1.5 h, 1.34 h and 84.29%, respectively. Pretreatment with metamizole caused a significantly decreased value for C _max 2.93 µg/ml) but the MAT value 2.23 h) was significantly increased. Statistically significant changes in the pharmacokinetic parameters of OLD following oral administration were also observed as a result of pretreatment with dexamethasone. The C _max was increased 8.24 µg/ml) and the t _max 0.5 h) and MAT 0.45 h) were lower.     

Evaluation method dependency of measured saturated hydraulic conductivity

Saturated hydraulic conductivity (Ks) is one of the most important hydraulic properties affecting water flow in soils. Spatial and seasonal variability as well as scale dependency are key factors which make it more difficult to accurately measure the saturated hydraulic conductivity. The uncertainty of the Ks values due to different evaluation methods was investigated using raw measured data obtained on two different Hungarian soils with three different in situ measuring devices (double ring, tension disc and mini disc infiltrometers), as well as with two laboratory methods. Since the very same raw infiltration data could result in significantly different Ks values, we have introduced the evaluation method dependency of the measured Ks values. Our investigations found that the effect of the applied evaluation method for assessing raw measured data can be just as significant as the effect of other factors, such as the scale effect, as well as the spatial and temporal variability.     

Pharmacokinetics of enrofloxacin in turkeys

The pharmacokinetics of enrofloxacin (EFL) and its active metabolite ciprofloxacin (CIP) was investigated in 7-8 month old turkeys (6 birds per sex). EFL was administered intravenously (i.v.) and orally (p.o.) at a dose 10 mg kg(-1) body weight. Blood was taken prior to and at 0.17, 0.33, 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 h following drug administration. The concentrations of EFL and CIP in blood serum were determined by high-performance liquid chromatography (HPLC). Serum concentrations versus time were analysed by a noncompartmental analysis. The elimination half-live and the mean residence time of EFL after i.v. injection for the serum were after oral administration 6.64+/-0.90 h, 8.96+/-1.18 h and 6.92+/-0.97 h, 11.91+/-1.87 h, respectively. After single p.o. administration, EFL was absorbed slowly (MAT=2.76+/-0.48 h) with time to reach maximum serum concentrations of 6.33+/-2.54 h. Maximum serum concentrations was 1.23+/-0.30 microg mL(-1). Oral bioavailability for for EFL after oral administration was found to be 69.20+/-1.49%. The ratios C(max)/MIC and AUC(0 --> 24)/MIC were respectively from 161.23+/-5.9 h to 12.90+/-0.5 h for the pharmacodynamic predictor C(max)/MIC, and from 2153.44+/-66.6 h to 137.82+/-4.27 h for AUC(0 --> 24)/MIC, for the different clinically significant microorganisms, whose values for MIC varies from 0.008 microg L(-1) to 0.125 microg mL(-1).