Bulldog Health
Bulldog Breeds
Multiple oral dosing of ketoconazole increases dog exposure to ivermectin
PURPOSE: The parasiticide ivermectin and the antimicrobial drug ketoconazole are macrolides that interact with P-glycoprotein. We investigated the effects of ketoconazole at a clinical dose on the pharmacokinetics of ivermectin, a CYP3A substrate with low hepatic clearance. METHODS: Beagle dogs received a single subcutaneous injection of ivermectin at 0.05 mg/kg alone (n=6) or in combination with a daily oral dose of ketoconazole 10 mg/kg over 5 days before and after ivermectin administration (n=6). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. RESULTS: Co-administered ketoconazole induced a higher plasma concentration and longer residence time of ivermectin in dogs, leading to a substantial increase in the overall exposure of the animal to the drug. Ketoconazole does not interfere with the production of the ivermectin metabolite but it may rather inhibit the elimination of the parental drug by interfering with P-gp transport. CONCLUSIONS: Multiple oral dosing of ketoconazole dramatically altered the pharmacokinetics of ivermectin in dogs leading to an increase in systemic exposure to the drug. Neurotoxicity of ivermectin means that inhibition of the P-gp function at the blood-brain barrier during polytherapy using P-gp inhibitors must be taken into consideration.
Clinique Vétérinaire des Lavandes, 26160 La Begude de Mazenc, France. INRA-UR66, Laboratoire de Pharmacologie-Toxicologie, BP 3, 31931 Toulouse Cedex 9, France.
Hugnet C, Lespine A, Alvinerie M.The Original Bulldog Club ->> The Bulldog Club of Milan ->>To promote and encourage the Breeding of Pure Bulldogs in all of the World, but more especially In the provinces of England, to Ireland, and in Scotland, in Italy, in Lombardy and in Milan.
Honorary President, Ever and Forever, Mrs. D.N. and Mr. Les Thorpe. Bulldog Club, creato per celebrare la incredibile nascita proprio a Milano, per merito esclusivo di Tuffnuts Bulldogs, in collaborazione con il The Bulldog International Research Center e con Ocobo Show Bulldogs, di quelli che, secondo i più profondi studi mondialmente dimostrabili, risulterebbero essere i più diretti discendenti e, quindi, i legittimi eredi di Rosa, il capostipite della Razza Bulldog, con genealogia integralmente inglese, Lincolnshire, Tuffnuts Ocobo. Il Club si è formato, infatti, nel Dicembre 2004 alla nascita di Tuffnuts Snow Angel Tuffnuts, dedicata al Maggiore L.A. Jackson ed a Dr. Les Cotton, il secondo Original Pure Breed Bulldog, nato a Milano ed in Italia dopo Tully, nato nel 2000, sempre nell ' Allevamento Tuffnuts Snow Angel. Per supportare la razza e tutti coloro che possiedono un Bulldog Inglese. Cucciolate disponibli, affidamento bulldogs, problemi di salute, riproduttori disponibili, etc..Il primo Club che si pone l'obiettivo di selezionare ed allevare anche il Bulldog Originale di Razza Pura, come era fino all' inizio del 20° secolo, con una genealogia completamente inglese, discendente dai più famosi Campioni della Storia.
