Determinación de las características farmacocinéticas y evaluación de residuos en leche de endectocidas (Moxidectina y Doramectina) en la especie caprina / Mª Sacramento Díaz Carrasco ; bajo la dirección de Michel Alvinerie... [et al.].

Tesis-Universidad de Murcia.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M. 1721.Consulte la tesis en: BCA. GENERAL. Fac. Veterinaria. Sala de estudio. Tesis-V 112

Le rôle des lipides et des lipoprotéines plasmatiques dans le transport et la pharmacocinétique des lactones macrocycliques (aspects pharmacologiques et toxicologiques)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Pour-on formulation of eprinomectin for cattle: fecal elimination profile and effects on the development of the dung-inhabiting diptera Neomyia cornicina (L.) (Muscidae)

International audienceThe plasma and fecal concentrations of eprinomectin were determined in cattle following topical administration at adose rate of 0.5 mg kg21. The maximum plasma concentrations of 12.24 ng ml21 occurred 2 d after administration, and eprinomectinremained detectable in plasma 29 d after administration (0.10 ng ml21). The maximum dung concentration of 350 ng g21 wasobserved 3 d after administration and thereafter for at least 29 d (4 ng g21). The amount of drug recovered in dung during thisperiod was 20.50% 6 4.31% of the total administered dose. The effects of eprinomectin against the nontarget dung-feeding DipteraNeomyia cornicina was assessed under laboratory conditions. Feces voided by cattle treated with eprinomectin were associatedwith high larval mortality during the first 12 d after treatment, with null emergence until day 7. The no-observed-effect concentrationfor N. cornicina was estimated to be close to 7 6 5 ng g21

Determination of selamectin in dog plasma by high performance liquid chromatography with automated solid phase extraction and fluorescence detection

A method is described for the determination of selamectin in dog plasma, using High-Performance Liquid Chromatography (HPLC) with fluorescence detection (excitation and emission wavelengths fixed at 355 and 465 nm, respectively). The fluorescent derivative was obtained by condensation reaction with trifluoroacetic anhydride and N-methylimidazole. The method employs 1 mL plasma samples and gives linear calibration graphs ($r = 0.999$) over the concentration range studied ($0.5 - 50$ ng$\cdot$mL$^{-1}$). Automatic solid phase extraction using the benchmate procedure was used for sample preparation. This method permits the determination of selamectin at levels as low as 0.1 ng$\cdot$mL$^{-1}$ and its suitability was demonstrated by a pharmacokinetic study on a dog receiving the therapeutic dose (Spot-on administration).Dosage de la sélamectine dans le plasma de chien par chromatographie liquide haute performance avec une extraction en phase solide automatisée et une détection fluorimétrique. Cet article décrit une technique analytique qui permet de doser la sélamectine dans le plasma par chromatographie liquide haute performance, après formation d'un dérivé fluorescent ($\lambda_{{\rm max}}$ excitation = 355 nm et $\lambda_{{\rm max}}$ émission = 465 nm). Ce dernier composé est obtenu grâce à une réaction de condensation utilisant l'anhydride de l'acide trifluoroacétique et le N-méthylimidazole. La technique requiert 1 mL de plasma et la courbe de calibration obtenue est linéaire dans la gamme de concentrations étudiée ($0.5 - 50$ ng$\cdot$mL$^{-1}$). Une extraction en phase solide automatisée a été employée pour traiter les échantillons. Cette méthode présente une limite de détection de 0.1 ng$\cdot$mL$^{-1}$ et apparaît efficace pour conduire des études de pharmacocinétique dans différentes espèces. Un exemple de cinétique plasmatique chez le chien ayant reçu une dose thérapeutique de sélamectine (Spot-on) est décrite

ABC transporter modulation: a strategy to enhance the activity of macrocyclic lactone anthelmintics

The emergence of parasites resistant to anthelmintic macrocyclic lactones (MLs) threatens to severely limit current parasite control strategies. Improving the current ML-based chemotherapy to perpetuate the efficacy of this broad-spectrum class of anthelmintics would be advantageous. In recent years it has become evident that the absorption, distribution and elimination of the MLs in hosts and parasites are under the control of multidrug resistance transporters (MDRs) such as P-glycoproteins. Theoretically, the inhibition of these transporters should result in an increase of the drug concentration in the organisms and higher treatment efficiency. This opinion article will discuss the recent findings in this research field and assess the possibilities of this approach being used in the field

New screening test to predict the potential impact of ivermectin-contaminated cattle dung on dung beetles

According to European Union recommendations, a test method has been developed to evaluate the effects of veterinary pharmaceuticals on dung feeding insects. This test method was evaluated with the dung beetle Aphodius constans by using fecal residues of ivermectin after a pour-on administration. Dung of different age (and thus containing different concentrations of ivermectin) as well as mixtures of highly-contaminated spiked dung with untreated control dung were studied in five test runs in two laboratories. The concentration of ivermectin (active substance; a.s.) in the dung samples was verified analytically. The main test endpoint was the survival of first instar larvae. The LC$_{50}$ using dung directly obtained from treated cattle ranged from 470 to 692 $\mu$g a.s. kg$^{-1}$ dung (dry weight; d.w.) and 67 to 97 $\mu$g a.s. kg$^{-1}$ dung (fresh weight; f.w.). Using mixtures, the outcome of two tests was almost identical: 770 to 781 $\mu$g a.s. kg$^{-1}$ dung (d.w.); 109 to 132 $\mu$g a.s. kg$^{-1}$ dung (f.w.). In comparison to the LC$_{50}$ values obtained when ivermectin was spiked in control dung at several concentrations (LC$_{50}$ 880–985 $\mu$g a.s. kg$^{-1}$ dung (d.w.)), the LC$_{50}$ values were again very similar. Three conclusions can be drawn from these results. The proposed test method seems to be robust and allows for the initiation of an international validation process (including ringtesting). Because of only small differences found in tests in which the test substance was spiked into control dung and those in which dung from treated cattle was applied, the use of a standard test method is proposed. The effects of ivermectin on ecologically relevant dung beetles obtained in a standardised test method reflect the results from field studies and are in the range of environmentally relevant concentrations

Toxicity of four veterinary parasiticides on larvae of the dung beetle Aphodius constans in the laboratory

International audienceThe environmental risk assessment of veterinary pharmaceuticals for dung beetles is strongly hampered because no standardized test method is available so far. Therefore, a test with the temperate dung beetle species Aphodius constans was developed. The survival of beetle larvae was determined after exposure to four veterinary parasitical pharmaceuticals (ivermectin, moxidectin, dicyclanil, and praziquantel) representing different treatment regimes, modes of action, and effect levels. The test was performed in the laboratory (three week duration) with fresh dung, as well as formulated (dried, ground, and rewetted) dung as test substrate (i.e., at least one range-finding test, two definitive test runs per pharmaceutical). Ivermectin was the most toxic substance (median lethal concentration [LC50] = 0.88–0.98 mg of active substance per kilogram of dung dry weight [mg a.s./kg dung (dry wt)] followed by dicyclanil (LC50 = 1.5–6.0 mg a.s./kg dung [dry wt]) and moxidectin (LC50 = 4.0–5.4 mg a.s./kg dung [dry wt]), whereas praziquantel showed very low toxicity (LC50 > 1,000 mg a.s./kg dung [dry wt]). The toxicity in fresh and formulated dung differed by a factor of between 1.1 and 4. The comparison with literature data on toxic effects of these substances on dung beetles in the laboratory or in the field is difficult because no results for praziquantel and dicyclanil have been published so far. With the use of data from ivermectin and moxidectin, the test results are on the same order of magnitude as those known from other studies. On the basis of the experiments reported here, it is recommended that this test be standardized in an international ring test so that it can be incorporated into the risk assessment process as described in the respective international guidelines for the registration of veterinary pharmaceuticals