The major metabolite from the use of furazolidone (FZD) in mammals, birds and fish is 2,3-dihydro-3-cyanomethyl-2-hydroxy-5-nitro-1alpha, 2-di(2-oxo-oxazolidin-3-yl)iminomethyl-furo [2,3-b]furan, also called 3-amine-2-oxazolidone (AOZ). A minor metabolite was identified as N-(5-amine-2-furfuryliden)-3-amine-2-oxazolidone (FOZ). To assess the potential carcinogenicity of FZD and the metabolic mixture of AOZ/FOZ, 11 mg FZD/ kg feed/day was fed for 12 weeks to mollies (Poecilia formosa), an ornamental fish species prone to develop tumors. The rate of tumors was quantified and defined both in mollies and their offspring. Then, some fish was made into fishmeal and incorporated into fish food at 500 g of meal/kg of food and fed to other mollies for 12 weeks. The rate of tumors was assessed. A similar trial design was carried out in tilapia fish (Oreochromis niloticus) by adding 50 mg FZD/kg to the feed for 90 days. All animals were placed in glass fishponds under controlled laboratory conditions. Each week, a significant biomass was collected from both groups to assess the macroscopic and histopathological changes. All mollies developed melanohistiocytomic tumors in the liver and other organs. Offspring from surviving mollie females stimulated to breed showed no changes compared to control animals. None of the mollies fed with the mollie-meal food contaminated with AOZ/FOZ developed tumors. Neither tilapia medicated with FZD nor tilapia fed with tilapia-meal contaminated with AOZ/FOZ developed tumors. These results do not support the established viewpoint that FZD must be banned from trophic chains based on its potential carcinogenic properties.

Pharmacokinetic/pharmacodynamic (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2H2O (Enro-C), as well as Monte Carlo simulations based on composite MIC50 and MIC90 (MIC, minimum inhibitory concentration) vs. Leptospira spp., were carried out in dogs after their intramuscular (IM) or oral administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by means of high-performance liquid chromatography. Maximum plasma concentration values after oral administration were 1.47 ± 0.19 µg/mL and 5.3 ± 0.84 µg/mL for Enro-R and Enro-C, respectively, and 1.6 ± 0.12 µg/mL and 7.6 ± 0.93 µg/mL, respectively, after IM administration. Areas under the plasma vs. time concentration curve in 24 h (AUC0–24) were 8.02 µg/mL/h and 36.2 µg/mL/h for Enro-Roral and Enro-Coral, respectively, and 8.55 ± 0.85 µg/mL/h and 56.4 ± 6.21 µg/mL/h after IM administration of Enro-R and Enro-C, respectively. The PK/PD ratios and Monte Carlo simulations obtained with Enro-C, not Enro-R, indicated that its IM administration to dogs will result in therapeutic concentrations appropriate for treating leptospirosis. This is the first time enrofloxacin has been recommended to treat this disease in dogs.

SummaryThe success rate in treatment against Staphylococcus aureus mastitis with antibacterial drugs is marginal. Low antibacterial drug concentrations in the mammary tissue is part of the reason for this failure. Enrofloxacin has only been administered on few occasions through the intramammary route i.e., combined with gentamicin in an undisclosed vehicle or dose. A new solvate form of enrofloxacin (enrofloxacin hydrochloride-dihydrate (enro-C)) prepared as 1.5% suspension pH 5.5 was tested in a field mastitis outbreak due to coagulase-negative S. aureus (CNS) in F1 (Holstein/Zebu) cows aged 5-8 years destined to be culled. Enro-C was administered intramammarily daily (300 mg/infected quarter) for 8 days both to healthy and mastitic cows; milk and serum enro-C concentrations were determined on days 1 and 8. Maximum serum concentration (C MAX ) values were similar in both groups (9.4 to 10.7 µg/mL). The area under the moment curve (AUMC) for enrofloxacin increased only by 11% in healthy cows and by 10% in infected cows from day 1 to day 8, a fact that suggests little accumulation with this dose regime. Peak concentrations in milk ranged from 18.5 to 19.8 µg/mL on day 1 and from 20.2 to 22 µg/mL on day 8. Cure rates on day 21 after treatment were 75% (12 out of 16 cows) or 69.4% (26 out of 36 glands). Somatic cell counts and California mastitis test showed a positive trend in cured animals. Uniquely high milk enrofloxacin and ciprofloxacin concentrations were obtained after intramammary administration of enro-C. These concentrations seem effective for treating CNS mastitis. The feasibility of incorporating this experimental pharmaceutical preparation of enrofloxacin is discussed.

Considering the already known pharmacological features of cefotaxime, a study with two approaches of pharmacokinetics and clinical efficacy in septicaemic dogs was carried out. Pharmacokinetic variables were defined for doses of 10 mg/kg, and 20 mg/kg, utilising a quantitative bacteriological analysis. Values for half-life (T½ß) at 10 mg/kg were 0.8, 1.48 and 1.52 h for the i.v., s.c. and i.m. routes, respectively. Corresponding values for the 20 mg/kg dose for the same routes were 0.8, 1.49 and 1.53 h, respectively. Relatively fast clearance (ranging from 0.58 to 0.64 L/kg/h) allowed a maximum dose interval of 12 h. The above-stated doses of cefotaxime were administered i.v. to 40 cases of septicaemia, clinically divided into 20 moderately severe cases treated with 10 mg/kg i.v., of cefotaxime bid, and 20 severe ones, treated with 20 mg/kgi.v. of cefotaxime bid. Injections continued until a previously defined criterion of 'clinically recovered' was obtained. Thereafter, a follow-up treatment was established using the same dose and dose-interval but through the s.c. route. Due to the apparent volumes of distribution obtained (ranging from 0.48 to 0.51 L/kg), considering the overall clinical efficacy obtained (90% for the 10 mg/kg dose and 75% for the 20 mg/kg dose), and due to the rapid improvement observed after a few doses of the drug (1.8 to 2.5 doses to 'clinical improvement'), it is safe to postulate such doses of cefotaxime as excellent choices for the treatment of septicaemia in dogs.

Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.