title: Plasma disposition, milk excretion and parasitological efficacy of mebendazole in donkeys naturally infected by Cyathostominae.
abstract: Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body weight (MBZ 1) and at the double horse dosage 20 mg/kg body weight (MBZ 2). Blood and milk samples were collected at various times between 1h and 120 h post treatment and analyzed by high performance liquid chromatography with photodiode array detector. Individual FECs (Faecal Egg Counts) were performed on each animal before the treatment (day-3) and weekly from day 7 until day 56 post treatment using a modified McMaster technique. The plasma concentrations and systemic exposure of MBZ in donkeys were relatively lower compared with the other methylcarbamate benzimidazoles. Dose-dependent plasma dispositions of MBZ were observed at the increased dosage (10 mg/kg vs 20 mg/kg) in donkeys. MBZ was not detected in any milk samples at a dosage of 10 mg/kg. However, the parent drug reached 0.01 μg/ml peak milk concentration at 10.66 h and AUCmilk/AUCplasma value was 0.18 ± 0.02 at a dosage of 20 mg/kg bodyweight. This study indicated that per os administration of MBZ has a minimal disposition rate into the milk and may be used in lactating donkeys with zero milk-withdrawal period. The results of FECRT for both MBZ dosages were efficient (>95% efficacy) until day 28. This trial demonstrates that MBZ oral paste at horse dosage (10 mg/kg B.W.) was effective and safety for the treatment of Cyathostominae in donkeys. Therefore, similar dosage regimens of MBZ could be used for horses and donkeys.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Balikesir University, Balikesir, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Gokbulut
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Balikesir University, Balikesir, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Aksit
authors.affiliation: Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Santoro
authors.affiliation: Istituto Zooprofilattico Sperimentale Lazio e Toscana, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Roncoroni
authors.affiliation: Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Mariani
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Buono
authors.affiliation: CREA, Consiglio per la Ricerca in Agricoltura e l'analisi dell'Economia Agraria Bella, Potenza, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Rufrano
authors.affiliation: Istituto Zooprofilattico Sperimentale Lazio e Toscana, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fagiolo
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy. Electronic address: vincenzo.veneziano@unina.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Veneziano
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D018397:Equidae / Q000469:parasitology*; D005243:Feces / Q000469:parasitology; D005260:Female; D007774:Lactation / Q000187:drug effects*; D008463:Mebendazole / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D008892:Milk / Q000737:chemistry; D010270:Parasite Egg Count; D011897:Random Allocation; D017206:Strongylida Infections / Q000188:drug therapy / Q000662:veterinary*; D013320:Strongyloidea / Q000187:drug effects / Q000502:physiology
chemical_list: D000871:Anthelmintics; D008463:Mebendazole
keywords: Cyathostominae; Donkey; Efficacy; Mebendazole; Milk; Pharmacokinetics