Pharmaceutical Design of a Formulation of Enrofloxacin-Alginate and its Strategic Dosage to Achieve Mutant Prevention PK/PD Ratios in Broiler Chickens.

INTRODUCTION: The comparative pharmacokinetics (PK) and PK/pharmacodynamics (PD) ratios of a new pharmaceutical design of enrofloxacin-alginate in dried beads (EADBs) and the reference enrofloxacin 10% solution was determined in broiler chickens. Also, the same parameters were determined after administering enrofloxacin with a double dosing scheme (through drinking water and as an in-feed medication of EADBs). 500 Arbor-Acres broiler chickens were randomly divided into five groups (n=100), adjusting in all cases, a dose of 10 mg/kg based on water and feed intake as follows: group EADBsad-lib receiving enrofloxacin through EADBs added to their feed as dressing; group EADBsbolus forcing the beads into the proventriculus using a semi-rigid gavage; group Enroad-lib dosed through their drinking water; group Enrobolus also administered into the proventriculus by gavage; group Enrow&f administering 5 mg/kg as EADBs in their feed, plus 5 mg/kg of enrofloxacin through their drinking water. METHODS: The PK parameters and the key PK/PD ratios were determined (Cmax/MIC and AUC0-24/MIC). Only group Enrow&f could achieve the PK/PD ratios regarded as mutant-prevention. RESULTS: This trial is the first one in which an in-feed medication of enrofloxacin, combined with water dosing, can result in PK/PD parameters superior to those obtained after administering the drug through drinking water at a dose of 10 mg/kg. CONCLUSION: Contrary to expectations, groups Enroad-lib and Enrobolus failed to achieve the desired PK/PD ratios when the breakpoint was established at 0.5 µg/mL but did so when MIC was set at 0.1 µg/mL. In contrast, EADBsbolus and Enrow&f achieved an adequate AUC0-24/MIC ratio for both MIC levels.

Oral pharmacokinetics of a pharmaceutical preparation of florfenicol in broiler chickens.

Introduction: The use of florfenicol must follow particular pharmacokinetic/pharmacodynamic (PK/PD) ratios, i.e., it requires achieving serum concentrations at or slightly above the pathogen's minimum inhibitory concentration (MIC) during the dosing interval and that the ratio of area under the concentration vs. time curve (AUC)/MIC should be as high as possible (still undetermined for poultry). As an alternative to the standard soluble florfenicol that is administered to the flock through drinking water, florfenicol premix is often recommended as feed medication in Latin America. However, no particular pharmaceutical design has been proposed. Methods: This study compared the PK of two preparations of florfenicol in broiler chickens and pondered the possibility of each covering the referred PK-PD ratios as predictors of clinical efficacy. The preparations comprise a pharmaceutical form as FOLA pellets (F = bioavailability; O = optimum; and LA = long-acting) and the premix formulation. The former are small colored pellets with vehicles and absorption enhancers of florfenicol designed for long action, and the latter is the reference premix of the antibiotic. First, these two pharmaceutical forms of florfenicol were administered as oral boluses (30 mg/kg), aided by a probe. In a second trial of the dosing form, both pharmaceutical preparations of florfenicol were administered in feed and ad libitum (110 ppm; ~30 mg/kg). Results: In both cases, FOLA-florfenicol presented much higher relative bioavailability (3.27 times higher) and mean better residence time than florfenicol premix (two times high when forced as bolus dose). Consequently, FOLA-florfenicol possesses better PK/PD ratios than less sensitive pathogens, i.e., E. coli. It is proposed that if a metaphylactic treatment of a bacterial outbreak in poultry is implemented with florfenicol prepared as FOLA, better PK/PD ratios will be obtained than those of standard florfenicol premix. Discussion: Clinicians must confirm that feed consumption in the flock has not been affected by the particular disease if FOLA pellets of florfenicol are used.

Boar semen cryopreserved with trehalose-containing liposomes: disaccharide determination and rheological behaviour.

This study aimed to detect intracellular trehalose in boar sperm that were cryopreserved with liposomes and conduct an analysis of its effects on some characteristics of thawed sperm, including rheological properties. First, soybean lecithin cholesterol-based liposomes were produced and characterized in the presence of 300 mM trehalose. Next, semen samples were frozen in two freezing media: a control medium with 300 mM trehalose and an experimental medium supplemented with 300 mM trehalose and 10% liposomes, both of which were thawed and then studied to ascertain their integrity, motility, rheological response, and trehalose quantities by testing two methods of spermatic lysis via high-performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD). The results found spherical liposomes measuring 357 nm that were relatively stable in an aqueous medium and had an entrapment efficiency of 73%. An analysis of the cryopreserved ejaculates showed that their viability and motility did not significantly differ between groups (P > 0.05). The viscous response of the samples was influenced by the extracellular medium rather than by the freezing-thawing process, which resulted in a loss of interaction between the cells and cryoprotectants. Finally, intracellular trehalose levels were determined using HPLC-ELSD, with no differences observed (P > 0.05) when comparing both sperm lysis methods. The use of liposomes with trehalose appears to be a promising option for boar semen cryopreservation, with a marked effect on rheological properties. The proposed HPLC-ELSD method was effective for measuring trehalose in cryopreserved cell samples.

Higher Bioavailability of Calcium in Chickens With a Novel In-Feed Pharmaceutical Formulation.

Egg production and egg shell quality decrease toward the end of the first laying cycle in hens (approximately by week 80). Even so, farmers often choose to work a second cycle with them. Defective egg shell production has been mainly linked to a decrease in gastrointestinal absorption of calcium. Here we studied pharmaceutically-designed modified-release small pellets (FOLAs) containing calcium to improve calcium bioavailability (F). The influence of FOLA alone or with capsicum-oleoresin was studied in a total of 400 Bovans-White hens randomly divided into four groups of 20 laying hens each and with five replicates per group (n = 100) as follows: (1) control group (GC) receiving a diet containing basal levels of 4.1% of calcium-carbonate; (2) group GF treated as GC but with the same dose of calcium-carbonate in FOLA; (3) group GFc5 was treated as GF but with 6 ppm of capsicum-oleoresin (500,000 Scoville Heat Units [SHU]); and (4) group GFc10 treated as GFc5 but with 1,000,000 SHU capsicum-oleoresin. Plasma concentrations of calcium were determined during 5 days at predetermined times sampling more often on days 1 and 5 for blood plasma kinetics of calcium. Relative bioavailability (Fr) values based on the area under the serum calcium concentration vs. time curve (AUC) were obtained and compared to GC. The AUC was statistically different among all groups (P < 0.5), but the GFc10 had the greatest Fr (194%), with serum calcium concentrations ranging from 25.37 to 31.2 µg/dL. Calcium residence time (RT) between GC and GF showed no statistical differences while GFc5 and GFc10 had statistically superior RT values. Simultaneously, the number of shell-less eggs per group and their thickness was evaluated by utilizing the same groups but with 150 hens per group on 6 days. Shell-less eggs decreased to zero in Group GFc10 and produced eggs with the greatest shell thickness from day 2 onwards. The inclusion of calcium-carbonate in the pharmaceutical form FOLA induced higher serum calcium concentrations (GF, GFc5, and GFc10) particularly during the night-phase of the hen's cycle-this coincides with the time at which egg shell formation occurs.

Oral Plus Topical Administration of Enrofloxacin-Hydrochloride-Dihydrate for the Treatment of Unresponsive Canine Pyoderma. A Clinical Trial.

An outpatient clinical trial on unresponsive deep-bacterial canine pyoderma (UDCP), without a control group, is presented. The chosen treatment was implemented with a new crystal-solvate of enrofloxacin (enrofloxacin HCl-2H2O or enro-C), in a dual scheme, i.e., 10 mg/kg/day PO, plus its topical administration, prepared as 0.5% in an alginate gel, thrice per day. Fifty-five cases that were unsuccessfully treated previously with another antibacterial drug, were selected and then classified as severe or very severe, according to a clinical score tailored for this trial. Aerobic bacteriological cultures of skin lesions and antibacterial sensitivity tests, were performed. Hematological status, liver, and kidney functions were determined before and after treatment. A complete success was obtained in 32 severe and 23 very severe, cases. The main bacterial isolates were: Staphylococcus intermedius (19/99), Staphylococcus pseudintermedius (16/99), Staphylococcus epidermidis (15/99), Staphylococcus pyogenes (14/99), Staphylococcus saprophyticus, Streptococcus sp., and others including Pseudomonas aeruginosa (6/99). The average duration of treatment was 8.03 days ± 2.1 SD and 12.0 ± 2.4 days, for dogs with severe or very severe UDCP, respectively. The adverse effects caused by enro-C were inconsequential and the hematological tests showed no deviations from normality. The use of enro-C administered dually to treat UDCP, is considered safe and highly effective.