Disposition kinetics of gentamicin in normal and endometritic cows using a microbiological assay

Gentamicin concentrations in serum, urine and milk were assayed microbiologically after intramuscular and intrauterine administrations in normal and endometritic cows. Following intramuscular injections of 5 mg gentamicin/kg b. wt. 3 times daily for three consecutive days, the highest serum concentrations occurred 1 h post administration of each dose with absorption half-lives [t0.5(ab)] ranging from 0.23 to 0.30 h for normal cows and from 0.21 to 0.29 h for endometritic cows. The elimination half-lives [t0.5(beta)] ranged from 2.51 to 2.95 h (normal cows) and from 2.71 to 3.29 h (endometritic cows). Following intrauterine administration of 4 mg gentamicin/kg. b. wt. once daily for three consecutive days, the drug peaked in serum 2 h after each dose with [t0.5(ab)] ranging from 0.47 to 0.52 h (normal cows) and from 0.57 to 0.68 h (diseased cows), while the drug was eliminated faster in endometritic cows than in normal cows. The mean systemic bioavailability were (70%) and (30%) after intramuscular and intrauterine administration, respectively. To compare serum concentrations, gentamicin was assayed in urine and milk in high and low concentrations, respectively.     

Disposition kinetics and urinary excretion of ciprofloxacin in goats following single intravenous administration

We evaluated the pharmacokinetics of ciprofloxacin in serum (n = 6) and urine (n = 4) in goats following a single intravenous administration of 4 mg/kg body weight. The serum concentration-time curves of ciprofloxacin were best fitted by a two-compartment open model. The drug was detected in goat serum up to 12 h. The elimination rate constant (β) and elimination half-life (t_1/2β) were 0.446 ± 0.04 h^-1 and 1.630 ± 0.17 h, respectively. The apparent volume of distribution at steady state (Vd_ss) was 2.012 ± 0.37 l/kg and the total body clearance (Cl_B) was 16.27 ± 1.87 ml/min/kg. Urinary recovery of ciprofloxacin was 29.70% ± 10.34% of the administered dose within 36 h post administration. In vitro serum protein binding was 41% ± 13.10%. Thus, a single daily intravenous dose of 4 mg/kg is sufficient to maintain effective levels in serum and for 36 h in urine, allowing treatment of systemic, Gram-negative bacterial infections and urinary tract infections by most pathogens.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular administration in Angora goats.

Pharmacokinetics and bioavailability of enrofloxacin were determined after single intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight (BW) to 5 healthy adult Angora goats. Plasma enrofloxacin concentrations were measured by high performance liquid chromatography. Pharmacokinetics were best described by a 2-compartment open model. The elimination half-life and volume of distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 h and Vd(ss),1.2 to 1.5 L/kg, respectively). Enrofloxacin was rapidly (t1/2a, 0.25 h) and almost completely absorbed (F, 90%) after IM administration. Mean plasma concentrations of enrofloxacin at 24 h after IV and IM administration (0.07 and 0.09 microg/mL, respectively) were higher than the minimal inhibitory concentration (MIC) values for most pathogens. In conclusion, once-daily IV and IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in treatment of infectious diseases caused by sensitive pathogens.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular injection in rabbits.

The pharmacokinetics and bioavailability of enrofloxacin were determined after IV and IM administration of 5 mg/kg of body weight to 6 healthy adult rabbits. Using nonlinear least-squares regression methods, data obtained were best described by a 2-compartment open model. After IV administration, a rapid distribution phase was followed by a slower elimination phase, with a half-life of 131.5 +/- 17.6 minutes. The mean body clearance rate was 22.8 +/- 6.8 ml/min/kg, and the mean volume of distribution was 3.4 +/- 0.9 L/kg. This large volume of distribution and the K12/K21 ratio close to 1, indicated that enrofloxacin was widely distributed in the body, but not retained in tissues. After a brief lag period (6.2 +/- 2.86 min), IM absorption was rapid (4.1 +/- 1.3 min) and almost complete. The mean extent of IM absorption was 92 +/- 11%, and maximal plasma concentration of 3.04 +/- 0.34 micrograms/ml was detected approximately 10 minutes after administration.     

Pharmacokinetics of enrofloxacin following intravenous and intramuscular administration in Angora rabbits

The pharmacokinetic behaviour and bioavailability of enrofloxacin (ENR) were determined after single intravenous (iv) and intramuscular (im) administrations of 5mg/kg bw to six healthy adult Angora rabbits. Plasma ENR concentrations were measured by high performance liquid chromatography. The pharmacokinetic data were best described by a two-compartment open model. ENR pharmacokinetic parameters were similar (p>0.05) for iv and im administrations in terms of AUC0-infinity, t1/2beta and MRT. ENR was rapidly (t1/2a, 0.05 h) and almost completely (F, 87%) absorbed after im injection. In conclusion, the pharmacokinetic properties of ENR following iv and im administration in Angora rabbits are similar to other rabbit breeds, and once or twice daily iv and im administrations of ENR at the dose of 5mg/kg bw, depending upon the causative pathogen and/or severity of disorders, may be useful in treatment of infectious diseases caused by sensitive pathogens in Angora rabbits.     

Disposition of creatine kinase activity in dog plasma following intravenous and intramuscular injection of skeletal muscle homogenates

The fate of skeletal muscle-derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000 g and 105 000 g supernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavail-ability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports medicine.     

Pharmacokinetics of diclofenac in sheep following intravenous and intramuscular administration

OBJECTIVES: The aim of this work was to examine the pharmacokinetics of diclofenac (DCLF) in sheep after intravenous (IV) and intramuscular (IM) dosing. ANIMALS: Healthy male Najdi sheep. MATERIALS AND METHODS: Diclofenac (1 mg kg(-1)) was administered to ten clinically healthy-male Najdi sheep IV or IM (n = 5 each). Blood samples (5 mL) were collected and serum was separated for drug analysis by high-performance liquid chromatography with UV detection. Diclofenac pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS: Diclofenac is quickly eliminated from sheep with a terminal T(1/2lambda) of 2-3 hours for both routes of administration. Total DCLF clearance after IV and IM administration was 87.86 +/- 24.10 and 85.69 +/- 40.76 mL kg(-1) hour(-1) respectively. The absolute bioavailability of IM DCLF appears to be approximately 100%. CONCLUSIONS AND CLINICAL RELEVANCE: The drug should be administered two to three times daily in sheep by IM or IV injection to maintain therapeutic concentrations. Additional studies are needed to evaluate the route of elimination of DCLF in sheep including metabolites formation and the significance of enterohepatic circulation.     

Disposition kinetics of tylosin administered intravenously and intramuscularly in desert sheep and Nubian goats

The pharmacokinetic behaviour of tylosin was compared in five Desert sheep and five Nubian goats. The animals were given a single dose of 20% tylosin (15 mg/kg), either intravenously (i.v.) or intramuscularly (i.m.). Following i.v. administration, the volumes of distribution and the elimination half-life times were similar in both species, whereas in goats a greater volume of the central compartment and faster clearance were observed. For the i.m. route, similar pharmacokinetics were observed in both species. The bioavailability (f) of the drug in goats (0.84 +/- 0.11) was not significantly higher than that in sheep (0.73 +/- 0.08). The present study has shown that, despite the significant differences in some of the drug pharmacokinetic parameters between sheep and goats for the i.v. route, identical intravenous and intramuscular dosage regimens of tylosin may be recommended for the two species.     

Clorsulon pharmacokinetics in sheep and goats following oral and intravenous administration

Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/kg. A three-compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one-compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro-intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half-life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41% and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the urea under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported in goats.     

Disposition kinetics of florfenicol in goats by using two analytical methods

Florfenicol, a monofluorinated analogue of thiamphenicol, has antibacterial activity against a broad spectrum of bacterial strains, including enteric bacteria that are resistant to chloramphenicol and thiamphenicol. The pharmacokinetics of florfenicol was studied following a single intravenous bolus or intramuscular injections at a dose of 20 mg/kg body weight, in five healthy goats. Serum florfenicol concentrations were determined using two analytical methods: microbiological assay and high-performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using redundant routine equations and the results derived from each method were compared. While florfenicol was detected for up to 4 and 8 h after administration by the bioassay, the drug was recovered in serum after 12 and 24 h by HPLC following intravenous and intramuscular injections, respectively. Comparison of the concentration profiles obtained by the two methods revealed substantial differences in the resultant kinetic data. Values for the initial serum concentration, elimination half-life, the area under the serum concentration-time curve, the mean residence time, and the systemic bioavailability were significantly (P < 0.01) higher when florfenicol concentrations were determined using HPLC. In conclusion, differences between analytical methodologies should be considered when interpreting the kinetic data for clinical use. However, both the hepatic biotransformations and the interchangeability of enantiomers need further investigation.     

Disposition of cyadox in domesticated cats following oral,intramuscular, and intravenous administration

Cyadox (CYX) is a synthetic antibacterial agent of quinoxaline with much lower toxic effects. A safety criterion of CYX for clinical use was established by studying the pharmacokinetics and metabolism of CYX after oral (PO), intramuscular (IM), and intravenous (IV) administration. CYX was administered in six domesticated cats (three males and three females) by PO (40 mg/kg.b.w.), IM (10 mg/kg.b.w.), and IV (10 mg/kg.b.w.) routes in a crossover pattern. Highly sensitive liquid chromatography with ultraviolet detection (HPLC-UV) method was developed for detection of CYX and its metabolites present in plasma, urine, and feces. The bioavailability of CYX after PO and IM routes was 4.37% and 84.4%. The area under curves (AUC), mean resident time (MRT), and clearance (CL) of CYX and its metabolites revealed that CYX quickly metabolized into its metabolites. The total recovery of CYX and its main metabolites was >60% after each route. PO delivery suggesting first pass effect in cats that might make this route suitable for intestinal infection and IM injection could be better choice for systemic infections. Less ability of glucuronidation did not show any impact on CYX metabolism. The findings of present study provide detailed information for evaluation of CYX.     

Therapy trials with enrofloxacin (Baytril) in a laying hen flock with Salmonella pullorum infections

The course of a disease due to Salmonella pullorum in laying chickens is described. The experimental application of enrofloxacin (Baytril) at a dosage of 100 mg/l drinking water for 10 days resulted in a stop of the mortality rate, increment of egg production and reduction of Salmonella excretion. A recurrence of the disease was observed in the fifth week following the end of treatment with high mortality and decreasing egg laying. The treatment lead to a short-dated success but a permanent elimination of the germ from the flock was not achieved.     

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 ± 0.72 µg/ml, which declined to 0.22 ± 0.01 µg/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 ± 0.46/h), and by the drug''s rate of transfer constant from the central to the peripheral compartment, K₁₂ (4.94 ± 0.31/h). The elimination halflife and the volume of distribution were 2.14 ± 0.02 h and 0.42 ± 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (Cl_B) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 ± 0.002 l/kg/h and 1.73 ± 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred.     

Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep

OBJECTIVE: To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. ANIMALS: 5 mature Katahdin ewes weighing 42 to 50 kg. PROCEDURE: Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 microg/ml, respectively. Median Cmax of the multiple-dose regimen was 2.99 microg/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC < or = 0.29 microg/ml.     

Disposition of oxfendazole in goats and efficacy compared with sheep

The disposition of intraruminally administered oxfendazole (OFZ) in goats was studied at 5, 10 and 20 mg kg-1. The area under the plasma concentration with time curve (AUC) increased with increasing dose but at a declining rate. AUC was lower after intra-abomasal compared with intraruminal administration. OFZ was less effective against drug resistant Trichostrongylus colubriformis in goats than in sheep but was of similar efficacy against drug resistant Haemonchus contortus in both host species. In the same experiment peak plasma levels of OFZ in goats were about half those in sheep given the same dose. Of 70 goats tested in the field, total rumen bypass occurred in 12 per cent and partial bypass in 67 per cent. Lower systemic availability due to bypass would be expected to reduce further anthelmintic efficacy in goats. From the results of these experiments a dose rate of 10 mg kg-1 is recommended for goats. When given at this rate as a divided dose at 12 hourly intervals over 24 hours, OFZ was significantly more effective than a single dose in reducing egg counts.