Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats.

Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 µg/kg) and buprenorphine (20 µg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 µg/kg) combined with buprenorphine (20 µg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.

The newly described mecA homologue, mecALGA251, is present in methicillin-resistant Staphylococcus aureus isolates from a diverse range of host species.

OBJECTIVES: A previously unidentified mecA homologue, mecA(LGA251), has recently been described in methicillin-resistant Staphylococcus aureus (MRSA) from humans and dairy cattle. The origin and epidemiology of this novel homologue are unclear. The objective of this study was to provide basic descriptive information of MRSA isolates harbouring mecA(LGA251) from a range of host animal species. METHODS: A number of S. aureus isolates from historical animal isolate collections were chosen for investigation based on their similarity to known mecA(LGA251) MRSA isolates. The presence of mecA(LGA251) was determined using a multiplex PCR and antimicrobial susceptibility testing performed by disc diffusion. RESULTS: MRSA harbouring mecA(LGA251) were found in isolates from a domestic dog, brown rats, a rabbit, a common seal, sheep and a chaffinch. All of the isolates were phenotypically MRSA, although this depended on which test was used; some isolates would be considered susceptible with certain assays. All isolates were susceptible to linezolid, rifampicin, kanamycin, norfloxacin, erythromycin, clindamycin, fusidic acid, tetracycline, trimethoprim/sulfamethoxazole and mupirocin. Five multilocus sequence types were represented (2273, 130, 425, 1764 and 1245) and six spa types (t208, t6293, t742, t6594, t7914 and t843). CONCLUSIONS: The discovery of MRSA isolates possessing mecA(LGA251) from a diverse range of host species, including different taxonomic classes, has important implications for the diagnosis of MRSA in these species and our understanding of the epidemiology of this novel mecA homologue.

Anti-infective DNase I coatings on polydopamine functionalized titanium surfaces by alternating current electrophoretic deposition.

Implant-associated infections (IAIs) can cause serious problems due to the difficult-to-treat nature of the biofilms formed on the implant surface. In mature biofilms, the matrix, which consists of polysaccharides, proteins, lipids and extracellular DNA (eDNA), forms a protective environment for the residing bacteria, shielding them from antibiotics and host defenses. Recently, the indirect prevention of biofilm growth through the degradation of eDNA using an enzyme, such as deoxyribonuclease (DNase) I, has gained attention and is regarded as a promising strategy in the battle against IAIs. In this study, coatings of DNase I were applied on titanium implant materials and their anti-infective properties were investigated. First, the effectiveness of alternating current electrophoretic deposition (AC-EPD) as a novel processing route to apply DNase I on titanium was examined and compared with the commonly applied diffusion methodology (i.e. classic dipping). For the same processing time, the use of AC-EPD in combination with a polydopamine (PDA) coupling chemistry on the titanium electrode surface significantly increased the protein deposition yield as compared to classic dipping, thereby yielding homogeneous coatings with a thickness of 12.8 nm and an average surface roughness, Sa, of ∼20 nm. X-ray photoelectron spectroscopy confirmed the presence of peptide bonds on all DNase-coated substrates. Time-of-flight secondary ion mass spectrometry detected a more dense DNase I layer in the case of AC-EPD for electrodes coupled as anode during the high-amplitude half cycle of the AC signal. The enzyme activity, release kinetics, and shelf life of DNase I coatings were monitored in real-time using a quantitative qDNase assay. The activity of DNase I coatings produced using AC-EPD was three time higher than for coatings prepared by classic dipping. For both deposition methods, a high initial burst release was observed within the first 2 h, while some activity was still retained at the surface after 7 days. This can be explained by the stable attachment of a small fraction of DNase to the surface through covalent bonding to the PDA layer, while superimposing DNase deposits were only loosely bound and therefore released rapidly upon immersion in the medium. Interestingly, coatings prepared with AC-EPD exhibited a prolonged, gradual release of DNase activity. The AC-EPD DNase coatings significantly reduced biofilm formation of both Staphylococcus epidermidis and Pseudomonas aeruginosa up to 20 h, whereas DNase coatings prepared by short classic dipping only reduce S. epidermidis biofilm formation, and this to a lesser extent as compared to AC-EPD DNase coatings. Overall, this study indicates that AC-EPD allows to rapidly concentrate DNase I on PDA-functionalized titanium, while maintaining the enzyme activity and anti-infective ability. This highlights the potential of AC-EPD as a time-efficient coating strategy (as opposed to the much slower dip-coating methodologies) for bioactive molecules in a wide variety of biomedical applications.

Developing a safe antifungal treatment protocol to eliminate Batrachochytrium dendrobatidis from amphibians.

Batrachochytrium dendrobatidis is one of the most pathogenic microorganisms affecting amphibians in both captivity and in nature. The establishment of B. dendrobatidis free, stable, amphibian captive breeding colonies is one of the emergency measures that is being taken to save threatened amphibian species from extinction. For this purpose, in vitro antifungal susceptibility testing and the development of efficient and safe treatment protocols are required. In this study, we evaluated the use of amphotericin B and voriconazole to treat chytridiomycosis in amphibians. The concentration at which the growth of five tested B. dendrobatidis strains was inhibited was 0.8 µg/ml for amphotericin B and 0.0125 µg/ml for voriconazole. To completely eliminate a mixture of sporangia and zoospores of strain IA042 required 48 h of exposure to 8 µg/ml of amphotericin B or 10 days to 1.25 µg/ml of voriconazole. Zoospores were killed within 0.5 h by 0.8 µg/ml of amphotericin B, but even after 24 h exposure to 1.25 µg/ml of voriconazole they remained viable. Amphotericin B was acutely toxic for Alytes muletensis tadpoles at 8 µg/ml, whereas toxic side effects were not noticed during a seven-day exposure to voriconazole at concentrations as high as 12.5 µg/ml. The voriconazole concentrations remained stable in water during this exposure period. On the basis of this data, experimentally inoculated postmetamorphic Alytes cisternasii were sprayed once daily for 7 days with a 1.25 µg/ml solution of voriconazole in water which eliminated the B. dendrobatidis infection from all treated animals. Finally, treatment of a naturally infected colony of poison dart frogs (Dendrobatidae) using this protocol, combined with environmental disinfection, cleared the infection from the colony.

Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs.

The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)-administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra-high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter-dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 µg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (µg/mL) can be predicted taking into account the OTC concentrations in plasma (µg/mL), according to the following equation: OTC(nasal secretions) = 0.28 OTC(plasma) -1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single-dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non-compartmental analysis. In plasma, the maximum concentration of drug (C(max) ), the time at which this maximum concentration of drug (T(max) ) was reached, the elimination half-life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 µg/mL, 4.0, 5.1 h and 150 µg·h/mL. In nasal secretions, C(max) , T(max) , t½ and AUC were, respectively, 6.29 µg/mL, 4.0, 6.6 h and 51.1 µg·h/mL.

Voriconazole, a safe alternative for treating infections caused by the Chrysosporium anamorph of Nannizziopsis vriesii in bearded dragons (Pogona vitticeps).

Dermal and systemic infections caused by the Chrysosporium anamorph of Nannizziopsis vriesii (CANV) are highly prevalent in reptiles and may result in severe disease and high mortality. Due to the high incidence of therapeutic failures, optimizing treatment is required. We first determined in this study the minimal inhibitory concentrations (MIC) of itraconazole, voriconazole, amphotericin B and terbinafine against 32 CANV isolates. For voriconazole, amphotericin B and terbinafine a monomodal MIC distribution was seen, whereas a bimodal MIC distribution was present for itraconazole, indicating acquired resistance in one isolate. Fourteen naturally-infected bearded dragons (Pogona vitticeps), from the same owner, were treated orally with either itraconazole (5 mg/kg q24h) or voriconazole (10 mg/kg q24h). The clinical condition, drug plasma concentrations and the presence of CANV in skin samples were followed. The animals were treated until complete clearance of the fungus. The plasma concentrations of voriconazole and itraconazole exceeded the minimal inhibitory concentrations of the CANV isolates. Elimination of CANV was achieved on average after 27 and 47 days of treatment with itraconazole and voriconazole, respectively. Whereas only 2 out of 7 survived after itraconazole treatment, only a single animal died in the voriconazole treated group. In conclusion, based on a limited number of animals, voriconazole applied at a regimen of 10 mg/kg bodyweight (BW) q24h seems to be a safe and effective antimycotic drug to eliminate CANV infections in bearded dragons.

Penetration of enrofloxacin into the nasal secretions and relationship between nasal secretions and plasma enrofloxacin concentrations after intramuscular administration in healthy pigs.

The pharmacokinetic behaviour of enrofloxacin (ENRO) in plasma and nasal secretions of healthy pigs was investigated, after a single-dose intramuscular administration of 2.5 mg/kg body weight of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. Concentrations of ENRO and its active metabolite ciprofloxacin (CIPRO) were determined in plasma and nasal secretions by high-performance liquid chromatography (HPLC). CIPRO was not detected probably because we investigated young weaned pigs. The data collected in 12 pigs for ENRO were subjected to noncompartmental analysis. In plasma, the maximum concentration of drug (C(max)), the time at which this maximum concentration of drug (T(max)) was reached, the elimination half-life (t(1/2)(beta)) and the area under the concentration vs. time curve (AUC) were, respectively, 694.7 ng/mL, 1.0 h, 9.3 h and 8903.2 ngxh/mL. In nasal secretions, C(max), T(max), t(1/2)(beta) and AUC were, respectively, 871.4 ng/mL, 2.0 h, 12.5 h and 11 198.5 ngxh/mL. In a second experiment conducted in 10 piglets, the relationship between concentrations of ENRO measured in the plasma and the nasal secretions has been determined following single-dose intramuscular administration of 2.5, 10 or 20 mg/kg body weight of the drug. It has been demonstrated that, among several variables, i.e., (1) the dose administered, (2) the time between intramuscular injection and blood sampling, (3) the age, (4) the sex, (5) the animal body weight and (6) the plasma concentration of the drug, only the latter influenced significantly the ENRO concentration in nasal secretions. Practically, using a generalized linear mixed model, ENRO concentrations in the nasal secretions (microg/mL) can be predicted taking into account the ENRO concentrations in plasma (microg/mL), according to the following equation:

Designing voriconazole treatment for racing pigeons: balancing between hepatic enzyme auto induction and toxicity.

Aspergillosis is a major cause of mortality in captive birds and its prognosis is often poor due to treatment failure. Voriconazole is a novel triazole antifungal agent that may be useful for the treatment of this infection in birds as it has shown promise in other animal models of the disease. We examined the pharmacokinetic behaviour of voriconazole in racing pigeons (Columbia livia forma domestica). Intravenous, oral and aerosol administration were investigated in single (10 mg/kg BW PO; 10, 5, 2.5 mg/kg BW IV), multiple dose (10, 20 mg/kg BW PO q12h, q24h) and nebulization (15 min, 10 mg/ml NaCl 0.9%) experiments. Quantitative measurements of voriconazole in plasma, as well as in lung tissue, collected at several time points, were done with a validated high performance liquid chromatography method using ultraviolet detection. Designing a treatment schedule with voriconazole is complicated by dose-dependent pharmacokinetics and induction of its biotransformation. Moreover, hepatic changes were seen in the oral multiple dose regimen at 10 and 20 mg/kg BW twice a day. Taking all features into account our study suggests that the oral dosage schedules of 10 mg/kg BW twice a day or 20 mg/kg BW once a day could be most appropriate in treating pigeons with aspergillosis.

Controlling the photoluminescence of CdSe/ZnS quantum dots with a magnetic field.

We present an investigation of the photoluminescence of CdSe/ZnS quantum dots at high light intensity and in low magnetic fields. Upon increasing the magnetic field up to 90 G, the photoluminescence intensity drops. When decreasing the magnetic field back to zero the photoluminescence drop remains present. A plausible explanation is the Zeeman splitting of defect-associated energy levels under the influence of a magnetic field. The defect-trapped electrons may then be positioned at a metastable level, thereby reducing the number of recombinations. This effect may be used to control the luminescence of quantum dots.

Multiple oral dosing of valacyclovir in horses and ponies.

The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC(50)-value of 1.7 microg/mL, i.e. EC(50) of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC(50)-value of 3.0 microg/mL, i.e. EC(50) of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36-1.17 microg/mL and 0.11-0.23 microg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC(50)-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC(50).

Severe alopecia due to demodicosis in roe deer (Capreolus capreolus) in Belgium.

Demodex mites are part of the normal fauna of hair follicles of many, if not all, healthy mammal species. Normally these parasites live in harmony with their host, however in states of putative immunosuppression the acarids undergo excessive proliferation and cause clinical disease, which may be localised or generalised. This paper describes four cases of demodicosis in roe deer (Capreolus capreolus) with localised to generalised alopecia.

Effects of an adapted intravenous amiodarone treatment protocol in horses with atrial fibrillation.

REASON FOR PERFORMING STUDY: Good results have been obtained with a human amiodarone (AD) i.v. protocol in horses with chronic atrial fibrillation (AF) and a pharmacokinetic study is required for a specific i.v. amiodarone treatment protocol for horses. OBJECTIVES: To study the efficacy of this pharmacokinetic based i.v. AD protocol in horses with chronic AF. METHODS: Six horses with chronic AF were treated with an adapted AD infusion protocol. The protocol consisted of 2 phases with a loading dose followed by a maintenance infusion. In the first phase, horses received an infusion of 6.52 mg AD/kg bwt/h for 1 h followed by 1.1 mg/kg bwt/h for 47 h. In the second phase, horses received a second loading dose of 3.74 mg AD/kg bwt/h for 1 h followed by 1.31 mg/kg bwt/h for 47 h. Clinical signs were monitored, a surface ECG and an intra-atrial electrogram were recorded. AD treatment was discontinued when conversion or any side effects were observed. RESULTS: Three of the 6 horses cardioverted successfully without side effects. The other 3 horses did not convert and showed adverse effects, including diarrhoea. In the latter, there were no important circulatory problems, but the diarrhoea continued for 10-14 days. The third horse had to be subjected to euthanasia because a concomitant Salmonella infection worsened the clinical signs. CONCLUSION: The applied treatment protocol based upon pharmacokinetic data achieved clinically relevant concentrations of AD and desethylamiodarone. POTENTIAL RELEVANCE: Intravenous AD has the potential to be an alternative pharmacological treatment for AF in horses, although AD may lead to adverse drug effects, particularly with cumulative dosing.

Determination of amiodarone and desethylamiodarone in horse plasma and urine by high-performance liquid chromatography combined with UV detection and electrospray ionization mass spectrometry.

A rapid method for the quantification of amiodarone and desethylamiodarone in animal plasma using high-performance liquid chromatography combined with UV detection (HPLC-UV) is presented. The sample preparation includes a simple deproteinisation step with acetonitrile. In addition, a sensitive method for the quantification of amiodarone and desethylamiodarone in horse plasma and urine using high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is described. The sample preparation includes a solid-phase extraction (SPE) with a SCX column. Tamoxifen is used as an internal standard for both chromatographic methods. Chromatographic separation is achieved on an ODS Hypersil column using isocratic elution with 0.01% diethylamine and acetonitrile as mobile phase for the HPLC-UV method and with 0.1% formic acid and acetonitrile as mobile phase for the LC-MS/MS method. For the HPLC-UV method, good linearity was observed in the range 0-5 microg ml(-1), and in the range 0-1 microg ml(-1) for the LC-MS/MS method. The limit of quantification (LOQ) was set at 50 and 5 ng ml(-1) for the HPLC-UV method and the LC-MS/MS method, respectively. For the UV method, the limit of detection (LOD) was 15 and 10 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The LODs of the LC-MS/MS method in plasma were much lower, i.e. 0.10 and 0.04 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The LODs obtained for the urine samples were 0.16 and 0.09 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The methods were shown to be of use in horses. The rapid HPLC-UV method was used for therapeutic drug monitoring after amiodarone treatment, while the LC-MS/MS method showed its applicability for single dose pharmacokinetic studies.

Quantitative risk assessment of Campylobacter spp. in poultry based meat preparations as one of the factors to support the development of risk-based microbiological criteria in Belgium.

The objective of this study was to do an exercise in risk assessment on Campylobacter spp. for poultry based meat preparations in Belgium. This risk assessment was undertaken on the demand of the competent national authorities as one of the supportive factors to define risk-based microbiological criteria. The quantitative risk assessment model follows a retail to table approach and is divided in different modules. The contamination of raw chicken meat products (CMPs) was represented by a normal distribution of the natural logarithm of the concentration of Campylobacter spp. (ln[Camp]) in raw CMPs based on data from surveillance programs in Belgium. To analyse the relative impact of reducing the risk of campylobacteriosis associated with a decrease in the Campylobacter contamination level in these types of food products, the model was run for different means and standard deviations of the normal distribution of the ln[Camp] in raw CMPs. The limitation in data for the local situation in Belgium and on this particular product and more precisely the semi-quantitative nature of concentration of Campylobacter spp. due to presence/absence testing, was identified as an important information gap. Also the knowledge on the dose-response relationship of Campylobacter spp. was limited, and therefore three different approaches of dose-response modelling were compared. Two approaches (1 and 2), derived from the same study, showed that the reduction of the mean of the distribution representing the ln[Camp] in raw CMPs is the best approach to reduce the risk of Campylobacter spp. in CMPs. However, for the simulated exposure and approach 3 it was observed that the reduction of the standard deviation is the most appropriate technique to lower the risk of campylobacteriosis. Since the dose-response models used in approach 1 and 2 are based on limited data and the reduction of the mean corresponds with a complete shift of the contamination level of raw CMPs, demanding high efforts from the poultry industry, it is proposed to lower the standard deviation of the concentration of Campylobacter spp. in raw CMPs. This proposal corresponds with the elimination of the products that are highly contaminated. Simulation showed that eating raw chicken meat products can give rise to exposures that are 10(10) times higher than when the product is heated, indicating that campaigns are important to inform consumers about the necessity of an appropriate heat treatment of these type of food products.

Intravenous amiodarone treatment in horses with chronic atrial fibrillation.

Six horses without underlying cardiac disease were presented because of atrial fibrillation of between 5 and 12 months duration. These horses received an intravenous amiodarone treatment of 5mg/kg/h for 1 h followed by 0.83mg/kg/h for 23h and subsequently 1.9mg/kg/h for 30h. During treatment, clinical signs were monitored and a surface ECG and an intra-atrial electrogram were recorded. Infusion was discontinued when sinus rhythm or side effects occurred. Four horses successfully cardioverted, of which one showed symptoms of hind limb weakness and weight shifting. Two horses did not cardiovert and showed similar side effects. In all horses, side effects disappeared within 6h after termination of treatment. Cardiac side effects, such as pro-arrhythmia, were not seen in any of the horses. Total bilirubin slightly increased in three horses and normalised within four days. It was concluded that amiodarone has the potential to treat naturally occurring chronic atrial fibrillation in horses, although further research is needed to refine the infusion protocol.

Detection and disposition of tolmetin in the horse.

Non-steroidal anti-inflammatory drugs (NSAIDs) are prohibited by the International Federation of Horse Racing Authorities but are commonly used in veterinary practice. Plasma and urinary concentrations of the NSAID tolmetin were determined by a high-performance liquid chromatographic procedure with UV detection following oral administration of a dose of 1 g to six fasted untrained standard bred mares. With a limit of quantitation (LOQ) of 0.05 microg/ml tolmetin was present in plasma for 9-12 h post-administration. Maximum concentrations of 2.1+/-0.89 microg/ml were found after 0.7+/-0.25 h. The elimination half-life was 2+/-1.25 h. Plasma protein binding at concentrations of 0.25 and 2.5 microg/ml was 92+/-4.9 and 84+/-4.2%, respectively. As early as 1 h after dosage, tolmetin could be detected in unhydrolysed urine and remained detectable up to 48 h (LOQ=0.5 microg/ml). The maximum concentrations occurred 1.8+/-0.4 h after administration. The percentage of the dose excreted as unchanged tolmetin within 12 h was 58+/-7.9%. Neither conjugates nor metabolites could be detected under the experimental conditions studied. For confirmatory analysis in doping control, an LC-MS method was developed. Analysis was performed on an ion trap LC-MS system equipped with an ESI probe in positive MS(2) mode.

Pharmacokinetics and efficacy of amoxycillin in the treatment of an experimental Streptococcus bovis infection in racing pigeons (Columba livia).

The pharmacokinetics of amoxycillin in pigeons (Columba livia) and the efficacy of amoxycillin treatment in pigeon streptococcosis, were investigated. After intravenous administration of 150 mg.kg-1 amoxycillin, the drug plasma concentration-time profile fitted an open two-compartment model. Amoxycillin was quickly cleared from the circulation with a mean half-life of 66 min and showed a distribution volume of 0.9 L.kg-1. The absolute oral bioavailability of amoxycillin was 50.1%. A 5-day drinking water treatment with amoxycillin (1500 mg.L-1, corresponding to 112.0 mg.kg-1.day-1 during day-light hours) significantly reduced the postinoculation morbidity in pigeons experimentally infected with Streptococcus bovis, compared to untreated infected controls.

The use of a Daphnia magna bioassay for rapid screening of acute intoxications with insecticides in dogs and cats.

Sudden death due to acute insecticide intoxications occurs frequently in dogs and cats. The absence of characteristic lesions at autopsy often renders post-mortem diagnosis dependent on the analysis of samples taken from the carcase at autopsy. In the present study, a bioassay utilizing Daphnia magna was proposed and tested as a rapid screening method for acute intoxications in dogs and cats. The bioassay was shown to be highly sensitive for detecting carbamate and organophosphate insecticides in the stomach contents. Generally. the mean survival time of the waterfleas in the control group was 5.17 h (SD = 1.24) and in the intoxicated group 1.32 h (SD = 1.49). during a 6 h observation period. If a cut-off is set at 4 h, this Daphnia bioassay gave 5.5% false negative results and 18.2% false positive results. using the results of toxicological analyses as a gold standard.

Pharmacokinetics and oral bioavailability of sulfadiazine and trimethoprim in broiler chickens.

Sulfonamides and trimethoprim are chemotherapeutics that are extensively used in various animal species. Little information about the pharmacokinetics of these compounds in chickens exists in the literature. In this study, a new commercial formulation of sulfadiazine in combination with trimethoprim was administered both intravenously and orally, according to a crossover design, to healthy, 7-week-old broilers. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods, and pharmacokinetic parameters were calculated. After intravenous or oral administration of trimethoprim (6.67 mg/kg body weight) and sulfadiazine (33.34 mg/kg body weight), both active substances were rapidly eliminated from the plasma. There was a mean half-life of 1.61 h for trimethoprim and 3.2 h for sulfadiazine. The apparent volumes of distribution (2.2 and 0.43 L/kg, respectively, indicated that the tissue distribution of trimethoprim was more extensive than that of sulfadiazine. The oral bioavailability was approximately 80% for both components.