Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administrations of ceftiofur sodium to dairy goats

Twelve (12) lactating dairy goats (46–71 kg body wt at study initiation) were divided into four treatment groups and dosed with ceftiofur sodium at 1.1 mg ceftiofur free acid equivalents (CFAE)/kg or 2.2 CFAE/kg using a complete two route (intravenous, i.v.; intramuscular, i.m.), two-period crossover design, with a 2-week washout between injections. After another 2-week washout period, the goats were dosed with ceftiofur sodium i.m. for 5 consecutive days at either 1.1 or 2.2 mg CFAE/kg. The goats from the 2.2 mg/kg multiple dose group were dried off and the i.v. kinetic study repeated. After all injections, blood samples were obtained serially for determination of combined serum concentrations of ceftiofur and metabolites. After intravenous doses of 1.1 and 2.2 mg/kg, the harmonic means of the terminal phase half-lives were 171.8 and 233 min, respectively, for lactating does. The harmonic mean of the terminal phase half-life after an i.v. dose of 2.2 mg/kg in non-lactating does was 254 min. The AUC _0–∞ was significantly less and the clearance significantly greater during lactation. After i.m. doses of 1.1 and 2.2 mg/kg, the harmonic mean terminal phase half-lives were 163 and 156 min, respectively. The i.m. bioavailability of ceftiofur sodium in goats was 100%, and the AUC _0–∞ was dose-proportional from 1.1–2.2 mg CFAE/kg body weight. After five daily i.m. doses of ceftiofur sodium at either 1.1 or 2.2 mg CFAE, there was minimal accumulation of drug in serum as assessed by C _max, and serum concentrations were dose-proportional after the multiple dosing regimen.     

Permeability of the blood-milk barrier to methylene blue in cows and goats

A 2% aqueous solution of methylene blue was administered as a single intravenous (i.v.) bolus injection (10 mg/kg) to six lactating cows and seven lactating goats and as a continuous i.v. drip to five lactating goats. The same dose was administered as a 10% solution by intramammary infusion to five lactating goats. Blood and milk samples collected at various times after these treatments were assayed for the drug by a colorimetric method. Methylene blue, a highly charged molecule (pK_a<1), passed readily from blood into milk; drug concentrations in milk 4-36 h after the single i.v. bolus injection were higher than those in blood. When examined at constant methylene blue levels in blood, a milk-blood ratio of 5: 1 was observed. After intramammary infusion, the drug passed quickly into systemic circulation, peaked at 3 h and was still detectable in blood 12 h after infusion. The drug appeared in the urine within 1 5 min after intramammary infusion. The rapid movement of the drug across the blood-milk barrier cannot be explained on the basis of its known physicochemical properties or according to the pH-pK_a passive diffusion concept.     

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

Plasma pharmacokinetics and urine concentrations of meropenem in ewes

The pharmacokinetics of meropenem was studied in five ewes after single i.v. and i.m. dose of 20 mg/kg bw. Meropenem concentrations in plasma and urine were determined using microbiological assay method. A two-compartment open model was best described the decrease of meropenem concentration in plasma after an i.v. injection. The drug was rapidly eliminated with a half-life of elimination ( t _{1/2 β} ) of 0.39 ± 0.30 h. Meropenem showed a small steady-state volume of distribution [ V _d(ss)] 0.055 ± 0.09 L/kg. Following i.m. injection, meropenem was rapidly absorbed with a t _1/2ab of 0.25 ± 0.04 h. The peak plasma concentration ( C _max) was 48.79 ± 8.83  μ g/mL was attained after 0.57 ± 0.13 h ( t _max). The elimination half-life ( t _1/2el) of meropenem was 0.71 ± 0.12 h and the mean residence time ( MRT ) was 1.38 ± 0.26 h. The systemic bioavailability (F) after i.m. injection was 112.67 ± 10.13%. In vitro protein-binding percentage of meropenem in ewe's plasma was 42.80%. The mean urinary recoveries of meropenem over 24 h were 83% and 91% of the administered dose after i.v. and i.m. injections respectively. Thus, meropenem is likely to be efficacious in the eradication of many urinary tract pathogens in sheep.     

Comparative pharmacokinetic disposition of closantel in sheep and goats

The pharmacokinetic disposition of closantel was examined following intraruminal (i.r.) or intramuscular (i.m.) administration to adult Merino sheep and to adult and 3-month-old, suckling Angora goats. In adult goats the maximum concentration (C_max) and area under the plasma concentration with time curve ( AUC ) following 3.75, 7.5 and 15.0 mg closantel/kg given i.r. increased with dose however the time of C_max (r_max= 2.6d) in plasma was unaffected by dose rate. The elimination phase (K₁₀) of closantel was monoexponential with a half-life ( t _½) of 4.7d again unaffected by dose rate. Apart from a more rapid absorption phase and earlier T_max following 3.75 mg closantel/kg i.m., pharmacokinetic behaviour was similar to that following i.r. administration at 3.75 or 7.5 mg/kg. Although absorption rate was more rapid in kids after i.r. administration at 7.5 mg/kg, pharmacokinetic disposition of closantel was otherwise similar to that in adult goats. No closantel was detected in milk of treated does or in the plasma of their kids. I.R. closantel at 7.5 mg/kg was more slowly absorbed in goats than in sheep but C_max was similar in both species. However, K₁₀ t _½ was significantly shorter in goats (4d) than in sheep (14d). Faster elimination resulted in an almost three-fold lowering of AUC in goats and could dramatically reduce the sustained action of closantel in this species compared with sheep.     

Pharmacokinetics of erythromycin in nonlactating and lactating goats after intravenous and intramuscular administration

The objectives of this work were to compare the pharmacokinetics of erythromycin administered by the intramuscular (i.m.) and intravenous (i.v.) routes between nonlactating and lactating goats and to determine the passage of the drug from blood into milk. Six nonpregnant, nonlactating and six lactating goats received erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of administration. Milk and blood samples were collected at predetermined times. Erythromycin concentrations were determined by microbiological assay. Results are reported as mean +/- SD. Comparison of the pharmacokinetic profiles between nonlactating and lactating animals after i.v. administration indicated that significant differences were found in the mean body clearance (8.38 +/- 1.45 vs. 3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs. 3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22 +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant differences after the i.m. administration. Passage of erythromycin in milk was high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0-12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m. administrations respectively). We, therefore, conclude that lactation affects erythromycin pharmacokinetics in goats.     

Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows

The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives ( t _½el) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution ( V _ss) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90–120 min after i.v. and i.m. administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over ≈ 24 h.
  Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.     

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C _max), and areas under the concentration curve ( AUC_0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC_0– of 457 ± 66 ng±day/mL (± SD) and a mean C _max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC _0– of 475 ± 82 ng-day/mL and a mean C _max of 33.1 ± 9.0 ng/mL Absorption constants ( k _a) determined by modelling were 0.542 ± 0.336 day^-1after sc administration and 0.710 ± 0.357 day^-1after i.m. administration. The 90% confidence limits on the difference between mean AUC _0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C _max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T _max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.     

Pharmacokinetic parameters and milk concentrations of ketoprofen after administration as a single intravenous bolus dose to lactating goats

Six clinically normal lactating does were administered ketoprofen (2.2 mg/kg intravenously (i. v.)). Blood and milk samples were collected prior to and for 24 h after drug administration. Drug concentrations in serum and milk were determined by high performance liquid chromatography. Pharmacokinetic parameters from each goat were combined to obtain mean estimates (mean ± SD) of half-life of elimination ( t _½β) of 0.32 ± 0.14 h, systemic clearance ( Cl ) of 0.74 ± 0.12 L/kg· h, and volume of distribution at steady state ( V _ss) of 0.23 ± 0.051 L/kg. In milk, ketoprofen was unmeasurable by the method employed (level of detection 25 ng/mL) for all samples.     

Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows

Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milk were analysed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state ( V _ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t _1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V _ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V _ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t _1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t _1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t _1/2 as determined from milk, applying a urinary excretion rate model, was 47 ± 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.     

Characterization of the relationship between serum and milk residue disposition of ceftriaxone in lactating ewes

The present study was planned to investigate the serum disposition kinetics and the pattern of ceftriaxone elimination in milk and urine of lactating ewes (n = 6) following i.v. and i.m. administration. A crossover study was carried out in two phases separated by 15 days. Ceftriaxone was administered at a dosage of 10 mg/kg b.w. in all animals. Serum, milk and urine samples were collected between 0 and 72 h and a modified agar diffusion bioassay method was used to determine the percentage of protein binding and to measure serum, urine and milk concentrations of ceftriaxone. The drug was detected between 5 min and 48 h postdosing. Concentrations of 0.56 (10 h) and 0.52 (12 h), 0.22 (10 h) and 0.19 (12 h), and 2.18 (24 h) and 2.11 (48 h) mug/mL were measured in serum, milk and urine following i.v. and i.m. administration, respectively. Individual pharmacokinetic parameters were determined by fitting a two-compartment model to the serum and one-compartment open model to the milk concentration-time profiles. After i.v. dosing, the elimination rate constant and elimination half-life were 0.4 +/- 0.05/h and 1.75 +/- 0.02 h, respectively. The volume of distribution at steady state (V(dss)) of 0.28 +/- 0.15 L/kg reflected limited extracellular distribution of the drug with total body clearance (Cl(tot)) of 0.14 +/- 0.10 L/h/kg. Following i.m. administration, the mean T(max obs), C(max obs), t(1/2el) and AUC values for serum data were: 0.75 h, 23.16 +/- 2.94 microg/mL, 1.77 +/- 0.24 h and 67.55 +/- 6.51 microgxh/mL, respectively. For milk the data were: 1.0 h, 8.15 +/- 0.71 mug/mL, 2.2 +/- 0.34 h and 26.6 +/- 5.14 microgxh/mL, respectively. The i.m. bioavailability was 83.6% and the binding percentage of ceftriaxone to serum protein was 33%. Concentrations of ceftriaxone in milk produced by clinically normal mammary glands of ewes were consistently lower than in serum; the kinetic value AUC(milk)/AUC(serum) and C(max milk)/C(max serum) ratios was<0.4. These low values indicated poor distribution and penetration of ceftriaxone from the bloodstream to the mammary gland of lactating ewes following both routes.     

Florfenicol pharmacokinetics in lactating cows after intravenous, intramuscular and intramammary administration

Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C _max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C _max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.     

Pharmacokinetics of polymyxin B administered via the bovine mammary gland

Polymyxin B was infused into normal, chronically inflamed, and acutely inflamed quarters of the mammary gland of lactating cows at dosages ranging between 1 and 2 million units (100–200 mg) per quarter. Samples of milk from treated and non-treated quarters, jugular venous blood, subcutaneous abdominal (mammary) venous blood, and urine were collected at intervals after treatment and were assayed using microbiological test methods for polymyxin B concentrations. The drug was not absorbed from normal and chronically inflamed quarters; more than 90% of the infused dose was recovered in milk within 24 h after treatment, and drug residues were detected up to the ninth milking. Drug concentrations in milk from acutely inflamed quarters were significantly lower than in milk from normal quarters; 55% of the infused dose was recovered in the milk within 24 h after treatment. The drug was detected in milk from non-treated quarters, in blood from the subcutaneous abdominal vein, and in the urine during 36–48 h after acutely inflamed quarters were infused with the drug. These data indicate that polymyxin B is well distributed throughout, and is absorbed to a significant degree into the systemic circulation from the acutely inflamed udder.     

Pharmacokinetics of marbofloxacin in dogs after oral and parenteral administration

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h; Cl _B= 0.10 L/h.kg; V _area= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, C _max of 1.4 μg/mL was reached at t _max of 2.5 h. Mean AUC and C _max values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except t _max (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.     

Bioavailability and pharmacokinetics of ibuprofen in the broiler chicken

The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration-time profiles, following i.v. (25 mg/kg) dosing were best described by a 2-compartment model. After intravenous administration, the volume of distribution at steady-state ( V _d(ss)), the total systemic clearance ( Cl _B), the elimination half-life (t_1/2p) and the MRT were 0.303 L/kg, 482.3 ml/h-kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, the t _max and C _max were 0.37 h, and 42.2μg/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, the t _max and C _max were 0.31 h and 23.91 μg/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different disease states.     

Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits

Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t _1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t _1/2el), mean residence time, and maximum plasma concentration ( C _max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C _max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.     

Thiamphenicol pharmacokinetics in beef and dairy cattle

The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows. It was found that this drug is rapidly absorbed (1 5 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h^-1 and 84%, respectively. The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (V_d(area)) of approximately 0.9 l/kg. The micro-rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k₁₂ > k₂₁). Elimination from plasma is relatively rapid, with a biological half-life of about 1.75 h. Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and 12 h.     

Pharmacokinetics of gentamicin following single dose intravenous administration in normal and febrile goats

A pharmacokinetic study of gentamicin (5 mg/kg intravenous (i.v.)) was conducted first in cinically healthy female goats and then in the same goats after induction of fever by Escherichia coli endotoxin (0.2 μg/kg i.v.). Rectal temperature increased 1 to 1.5°C in febrile goats. Differences in the blood serum concentrations of gentamicin were not observed at any time between febrile and normal goats. The disposition kinetics of gentamicin were described by a biex-ponential expression C_P= Ae^-αt+ Be^-β. Median values for the half-lives of gentamicin were 103.6 min in normal and 136.0 min in febrile goats. The apparent volume of distribution (V_d) was 263.3 ml/kg in the febrile goats which was not different from that in the normal goats (240.6 ml/kg). The volume of the central compartment (V_c) was almost identical in normal and febrile goats. The body clearance (Cl_β) was observed to be 1.7 and 1.6 ml/min-kg in normal and febrile goats, respectively. Dosage regimens for gentamicin were calculated on the basis of median kinetic data.     

Pharmacokinetics of enrofloxacin after single intravenous, intramuscular and subcutaneous injections in lactating cows

Five Ayrshire cows were given enrofloxacin (5 mg/kg body weight) intravenously (i.v.), intramuscularly (i.m.) and subcutaneously (s.c). The antimicrobial activity was measured in milk and serum samples using the agar-diffusion technique. High-performance liquid chromatography (HPLC) assay was used to study the extent of metabolism of enrofloxacin to dprofloxacin. Analysis of the serum concentration-time data was based on statistical moment theory. Mean t _1/2β of antimicrobial activity in serum was 1.7, 5.9 and 5.6 h after i.v., i.m. and s.c. administration, respectively. Both i.m. and s.c. routes were associated with a marked flip-flop phenomenon. Based on HPLC analysis of serum samples, the half-lives of enrofloxacin and ciprofloxacin were approximately the same. A marked proportion of enrofloxacin was metabolized to ciprofloxacin. The enrofloxacin fraction bound in vitro to serum proteins was 36–45%. About 0.2% of the total enrofloxacin dose was found in milk during the first 24h and the amount transferred did not depend on the route of administration. Based on the HPLC data, enrofloxacin concentration in milk was parallel to that in serum, while ciprofloxacin was concentrated in milk. After i.v. injection, the peak concentration of enrofloxacin in milk was reached between 0.7 and 1.3 h but occurred much later for ciprofloxacin ( t _max 5–8 h). After i.m. and s.c. administration the concentration-time curves for both enrofloxacin and ciprofloxacin in milk were shallow and there were no obvious peaks.     

Suitability of lactate dehydrogenase activity and somatic cell counts of milk for detection of subclinical mastitis in Merino ewes (short communication).

The relationship between somatic cell counts (SCC) and LDH activity in milk was examined in Turkey to find out the suitability of these variables for early detection of subclinical mastitis in Merino ewes. A significant positive correlation was found between LDH activity and SCC in ewes' milk. LDH activity in milk samples appeared to be a sensitive and specific indicator of subclinical mastitis in ewes: it was significantly higher in milk from inflamed (mastitic) udders than in normal milk.