The pharmacokinetics of florfenicol (FF), thiamphenicol (TP) and chloramphenicol (CP) after single intravenous (i.v.) or oral (p.o.) administration was studied in an independent cross-over study in broiler turkeys. All the fenicol antibiotics were administered at a dose of 30 mg/kg b.w. and their concentrations in plasma samples were assayed using the same validated high-performance liquid chromatography method. Pharmacokinetic parameters were calculated by a noncompartmental method. The kinetic profiles of the compounds were compared with the results of the structure-activity relationship. According to the proposed mathematical description, no differences in plasma clearance values for the studied antibiotics were observed. The mean residence time values of FF, TF, and CP after i.v. injection were 3.37+/-0.63, 2.43+/-0.29, and 2.12+/-0.21 h, respectively. The mean values of Varea for FF (1.39+/-0.31 L/kg) and TP (1.31+/-0.19 L/kg) were similar, but significantly different from that of CP (1.04+/-0.12 L/kg). The bioavailabilities of FF, TP, and CP after oral administration were 82%, 69%, and 45%, respectively. Differences in the bioavailability values of the compared fenicol antibiotics correspond to the ratio of the apolar/polar surface areas of their particles.

Enrofloxacin is a concentration‐dependent antimicrobial used in bacterial infections in poultry. During a few months of a turkey's life, pharmacokinetics of drugs undergoes substantial changes which may compromise their efficacy due to variability in internal exposure (measured by area under the concentration–time curve, AUC). The aim of this study was to describe the effects of age on the pharmacokinetics of a single intravenous (i.v.) and oral administration of enrofloxacin at a dose of 10 mg/kg to turkeys. It was found that during a 2.5‐month‐long period of growth from 1.4 to 14.6 kg, the AUC after i.v. administration increased almost threefold due to a significant decrease in the body clearance (from a mean of 0.76–0.28 L hr−1 kg−1). Over the same period, the mean elimination half‐life was prolonged from 2.65 to 7.03 hr. Oral administration resulted in a similar trend in pharmacokinetic parameters. For both routes, formation of the major metabolite, ciprofloxacin, was marginal. Protein binding was not age‐dependent and never exceeded 50%. Body clearance, volume of distribution and elimination half‐life were subjected to an allometric analysis and a novel, nonlinear dosage protocol has been proposed to improve the internal exposure to the drug in different age groups of turkeys.

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The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half‐life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.

Whereas interspecies variation in pharmacokinetics is a commonly investigated issue, variations in drug kinetics within a species are less documented. The aim of the study was to assess the influence of age-related changes in haemodynamics on the pharmacokinetics of metronidazole (MTZ) and its hydroxy metabolite (MTZ-OH) in turkeys. MTZ was administered intravenously and orally at a dose of 25 mg/kg. Plasma drug and metabolite concentrations were assessed by high-performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. Haemodynamic parameters (heart rate, stroke volume, cardiac output) were assessed by echocardiography and extraction ratio for MTZ was calculated based on total body clearance (ClB ). Between the 5th and 15th week of age, ClB of MTZ decreased from 3.6 to 1.2 mL/min/kg causing a twofold increase in the mean residence time (MRT) and elimination half-life (T1/2el ). The MTZ-OH production decreased threefold and its MRT and T1/2el increased. Although heart rate significantly decreased with age, cardiac output increased. Extraction ratio was low in all age groups. It is concluded that significant age-dependent decrease in ClB of MTZ in turkeys resulted from decreased perfusion of the clearing organs and their reduced metabolic capacity. This phenomenon is probably species specific and may apply to other therapeutic agents.

1. The aim of this study was to determine if the pharmacokinetics (PK) of florfenicol (FF) undergo age-dependent changes in broilers. Since drug elimination depends on cardiovascular functions, a haemodynamic study was performed in parallel. 2. Broilers of 0.68, 1.27, 2.45 and 5.13 kg were administered FF in a single intravenous dose of 30 mg/kg body weight. Plasma drug concentrations were determined using high-performance liquid chromatography and PK parameters were calculated using a non-compartmental model. Echocardiography was used to measure haemodynamic functions. 3. During growth, the area under the drug concentration-time curve (AUC) increased from 25.7 ± 2.9 to 39.0 ± 8.0 mg h/l. Total body clearance (Cl) gradually decreased from 1.19 ± 0.14 to 0.80 ± 0.15 l/h/kg. Elimination half-life increased from 0.73 ± 0.08 to 1.07 ± 0.07 h, whereas volume of distribution (V) remained unchanged. Haemodynamic measurements revealed an increase in cardiac output, from 495 ± 65 to 1303 ± 306 ml/min, in the respective body weight groups. 4. Allometric models for PK and haemodynamic parameters were developed and validated. All models proved to be statistically significant; however, only models for Cl and V met stringent validation criteria. Model for Cl was used to calculate an optimal dose for a given age group that provides uniform AUC. 5. Age-dependent change in FF kinetics may cause variability in therapeutic response under clinical conditions. A novel approach to the dosing protocol was proposed as a means of optimising therapeutic efficacy.

KeyWords Capillary electrophoresis Streptomycin Eggs yolk Maximum residue limits SummaryA capillary electrophoresis method for the determination of streptomycin in eggs is described. Analyses were performed on an uncoated silica capillary using a buffer solution of 30mM sodium dihydrophosphate, 5 mM boric acid and 5 mM sodium tetraborate. Analytes were detected at 200 nm an the calibration curve was linear over the range of0.16 to 2.0/~g g 1 (r = 0.999). The total analysis time was 7 min. The method has been successfully applied to the quantitative determination of streptomycin in hen eggs after drug ingestion and could used for evaluation of maximum residue limits.

Background: Despite common use of tylosin in turkeys, the pharmacokinetic (PK) data for this drug in turkeys is limited. Within a few months of growth, PK of drugs in turkeys undergoes changes that may decrease their efficacy due to variable internal exposure. Objectives: The objective of this study was to investigate the influence of age on the PK of a single intravenous (i.v.) and oral administration of tylosin to turkeys at a dose of 10 and 50 mg/kg, respectively. Methods: Plasma drug concentrations were measured using high-performance liquid chromatography with UV detection. The PK parameters were assessed by means of noncompartmental approach and were subjected to allometric analysis. Results: During a 2.5-month-long period of growth from 1.4 to 14.7 kg, the median value for area under the concentration-time curve after i.v. administration increased from 2.61 to 7.15 mg × h/L and the body clearance decreased from a median of 3.81 to 1.42 L/h/kg. Over the same time, the median elimination half-life increased from 1.03 to 2.96 h. For the oral administration a similar trend was noted but the differences were less pronounced. Bioavailability was variable (5.76%-21.59%) and age-independent. For both routes, the plasma concentration of the major tylosin metabolite, tylosin D, was minimal. Protein binding was age-independent and did not exceed 50%. Allometric analysis indicated a relatively poor predictivity of clearance, volume of distribution and elimination half-life for tylosin in turkeys. Conclusions: Age has a significant impact on tylosin PK in turkeys and dosage adjustment may be needed, particularly in young individuals.