Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses

OBJECTIVE: To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. ANIMALS: 6 healthy mature horses. PROCEDURES: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. RESULTS: Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.     

Biliary elimination kinetics and tissue concentrations of oxytetracycline after intravenous administration in hens

The pharmacokinetics of the biliary elimination of oxytetracycline (OTC) and tissue concentrations in certain organs were studied in 10 Leghorn hens. The animals were anaesthetized using xylazine/ketamine administered by the intramuscular (i.m.) route and were immobilized for right laparotomy. Both bile ducts were cannulated and a dose of 20 mg/kg of oxytetracycline hydrochloride was administered intravenously (i.v.). Samples of bile excreted were taken at predetermined intervals during 6 h. At 6 h animals were slaughtered and tissue samples of blood, liver, kidney, pancreas, spleen, heart, lung and pectoral muscle were taken. The values for OTC biliary elimination rate times were best fitted to a one-exponential equation. The maximum value for OTC biliary excretion rate (3.69+/-0.6 microg/min/kg) was reached at approximately 17.5 min (time to maximum concentration (tmax)). The first-order rate constant for the biliary excretion (k) and the half-life (t1/2) were 6.7x10(-3) min(-1) and 110.55 min, respectively. The mean value of area under the biliary excretion rate time curve (AUC) indicated that 839.77 microg/kg body weight (b.w.) were eliminated by the biliary route. The cumulative biliary excretion data indicated that approximately 4.20% of the dose was eliminated by this route, 3.28% being eliminated during the first 6 h and 0.92% thereafter. The highest mean concentrations were found in the kidney (35.82 microg/kg) and liver (16.77 microg/g). Significant differences were found between the concentrations of the various tissues studied. Plasma concentration was lower than that of the other tissues (except lung).     

Pharmacokinetics of moxidectin and doramectin in goats.

The pharmacokinetic behaviour of doramectin after a single subcutaneous administration and moxidectin following a single subcutaneous or oral drench were studied in goats at a dosage of 0.2 mg kg(-1). The drug plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. Maximum plasma concentrations of moxidectin were attained earlier and to a greater extent than doramectin (shorter t(max) and greater C(max) and AUC than doramectin). MRT of doramectin (4.91 +/- 0.07 days) was also significantly shorter than that of moxidectin (12.43 +/- 1.28 days). Then, the exposure of animals to doramectin in comparison with moxidectin was significantly shorter. The apparent absorption rate of moxidectin was not significantly different after oral and subcutaneous administration but the extent of absorption, reflected in the peak concentration (C(max)) and the area under the concentration-time curve (AUC), of the subcutaneous injection (24.27 +/- 1.99 ng ml(-1) and 136.72 +/- 7.35 ng d ml(-1) respectively) was significantly greater than that of the oral administration (15.53 +/- 1.27 ng ml(-1) and 36.72 +/- 4.05 ng d ml(-1) respectively). The mean residence time (MRT) of moxidectin didn't differ significantly when administered orally or subcutaneously. Therefore low oral bioavailability and the early emergence of resistance in this minor species may be related. These results deserve to be correlated with efficacy studies for refining dosage requirements of endectocides in this species.     

Relationship between egg‐shell colour and two measurements of shell strength in the Vasca breed

1. Egg‐shell colour, egg specific gravity, shell thickness and egg weight were determined for 2080 eggs from three varieties of the Vasca, a Spanish brown‐egg‐laying hen.

2. Intermediate, positive and significant (P < 0·01) correlation coefficients were found between egg‐shell colour and specific gravity (0·25), or shell thickness (0·21). There was a very high (0·84), significant (P < 0·01) correlation between the measures of shell strength.

3. Shell thickness was accurately predicted with both specific gravity and egg weight as independent variables (determination coefficient 0·74); eggshell colour did not explain any further variation.

4. All traits showed considerable departure from normality in the form of negative kurtosis (shell colour and specific gravity), positive kurtosis (shell thickness and egg weight), negative skewness (shell thickness) or positive skewness (egg weight).

5. Egg‐shell colour, specific gravity and shell thickness were less in July, in old birds and in eggs laid in the morning. Differences in egg quality traits between the three varieties were not significant.

     

Pharmacokinetics of norfloxacin after intravenous,intramuscular and subcutaneous administration to rabbits

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross‐over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap‐frozen at ?45°C and analysed for norfloxacin concentrations using high‐performance liquid chromatography. The terminal half‐life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD ) 108.25 ± 12.98% and the C_max was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD ) 84.08 ± 10.36% and the C_max was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro‐organisms with MIC ≤0.14 or 0.11 μg/mL , respectively.     

Pharmacokinetics of deflazacort in rabbits after intravenous and oral administration and its interaction with erythromycin

The pharmacokinetic of deflazacort after intravenous and oral administration and the effect of erythromycin on the disposition of deflazacort in rabbits were investigated. A parallel study was carried out in twelve rabbits. The plasma concentration–time profiles of deflazacort were determined after intravenous and oral administration of single dosages of 5 mg/kg in the presence and absence (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21‐desacetyldeflazacort were determined by HPLC. Plasma concentration–time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The t_½λz values following intravenous and oral administration were 3.67 and 4.96 hr, respectively. The apparent volume of distribution at steady‐state (V_ss) was 4.08 ± 0.31 L/kg, this value indicates that deflazacort is widely distributed into the extravascular tissues. Moreover, bioavailability after oral administration of deflazacort (F = 87.48%) was high. Pharmacokinetic analysis after both routes of administration revealed a significant reduction in total body clearance, a significant increase in mean residence time, half‐life and plasma concentrations of the steroid in the presence of multiple dose erythromycin. The results indicated the influence of the erythromycin on deflazacort disposition, which is consistent with a pharmacokinetic‐type interaction in the elimination of the drug from the body. Moreover, this interaction should be considered to avoid adverse effects when using both drugs concomitantly.     

Multielemental analysis and classification of amaranth seeds according to their botanical origin

The characterization of amaranth seeds (Amaranthus spp.) was developed for Amaranthus hypochondriacus, Amaranthus cruentus, and Amaranthus dubius. The elemental concentrations were determined by inductively coupled plasma optic atomic spectroscopy. Pattern recognition methods were used for the characterization of seed samples: nonsupervised methods included principal components analysis and cluster analysis; supervised methods were linear discriminant analysis and partial least squares discriminant analysis (PLS-DA). Informed are the concentrations of the following elements: Ag, Al, Ba, Ca, Co, Cr, Cu, Fe, K, La, Li, Mg, Mn, Mo, Na, Ni, P, S, Sr, V, Zn, and Zr. The lowest mineral content was found in A. hypochondriacus, and the highest one was found in A. dubius. For the classification, selected variables for all multivariate methods were Ba, Cr, Li, Mn, Ni, S, and Sr. Nonsupervised methods allowed us to distinguish between the three species of amaranth; however, PLS-DA supervised methods showed the best prediction ability.     

Pharmacokinetics and tissue tolerance of azithromycin after intramuscular administration to rabbits

The pharmacokinetics of azithromycin after intravenous and intramuscular injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits by using a modified agar diffusion bioassay for determining plasma concentrations. The plasma creatine kinase activity was determined after i.m. administration for the evaluation of the tissue tolerance. The elimination half-lives of azithromycin after intravenous and intramuscular administration were 24.1 and 25.1h, respectively. After intramuscular administration mean peak plasma concentration was 0.26+/-0.01 mg/L and bioavailability was 97.7%. Plasma CK activity rose sharply within 8h after i.m. injection of azithromycin; activity returned to pre-treatment level by 48-72 h post-treatment. The transient rise in serum CK activity indicates some degree of muscle tissue damage at the injection site.     

Characterization of the aroma of a wine from maccabeo. Key role played by compounds with low odor activity values

An extract from a dry young wine from Maccabeo was studied by aroma extract dilution analysis (AEDA), quantitative gas chromatography, and different sensory studies. In a first study, 53 different aroma compounds were quantified and used to prepare aroma models. 2-Methyl-3-furanthiol (FD = 16) and 4-methyl-4-mercaptopentan-2-one (FD = 2), could not be quantified and were not included in those models, which were not very similar to the original wine. Omission tests did not show the existence of impact compounds. In another set of experiments, selected aroma chemicals were added to the original wine, but in only in two cases (isoamyl acetate and gamma-nonalactone) was a positive effect noted, on banana and citric notes, respectively. After these discouraging results, 4-methyl-4-mercaptopentan-2-one and 2-methyl-3-furanthiol were quantified and included in the models. The concentration of the former was as low as 5 ng x L(-)(1) (odor threshold = 0.8 ng x L(-)(1)); however, its inclusion in the synthetic mixture had a significant effect, making it very close to the original wine. Its role was confirmed by omission tests. Results are briefly discussed.