Universidad Nacional del Centro de la Provincia de Buenos Aires

Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, UNCPBA. Campus Universitario (7000) Tandil, Argentina.
Director: Prof. Dr Carlos E. Lanusse, e-mail: clanusse@vet.unicen.edu.ar

Personnel involved: Dr. Sergio Sánchez Bruni, Dr. Luis Alvarez, Dr Adrián Lifschitz , Dr. Guillermo Virkel, Dr. Laura Moreno, Dr Hugo Solana, Dr. Fernanda Imperiale, Dr. Lourdes Mottier , MV Juan Sallovitz (Graduate Student), MV Mariana Ballent (Graduate Student), MV Claudia Gonzalez, (Graduate Student), Lic. Laura Ceballos (Graduate student), Ftica Alejandra Pis (Research Assistant), Soledad Sazatornil (Administrative Assistant), Walter Barbieri (Technician).

Ongoing Research Program
PHARMACOLOGY OF ANTIPARASITIC DRUGS IN RUMINANTS

Most of the losses in livestock production are associated with gastrointestinal nematode, lungworm and liver fluke infestations, including the cost of chemically-based parasite control measures. Due to the magnitude of the investment in drug medications to control helminth parasites in ruminants in countries whose economies are heavily dependent on their livestock production, it is highly important to generate scientific information (locally produced) on how to improve the use of available anthelmintic molecules under field conditions to avoid/delay the development of parasite resistance, a serious inconvenient for countries of the southern hemisphere (such as Argentina) where animals graze on pasture all year around.

This is an overall research program in Veterinary Pharmacology addressed to search for different pharmacologically-based strategies for the optimization of parasite control in livestock, which has been under progress since 1992 in the Laboratorio de Farmacología, Dpto. Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Prov. de Buenos Aires, Argentina. The main research goal of the program is to characterise the relationship among plasma disposition kinetics, pattern of biotransformation, tissue distribution and the drug-parasite interaction for antiparasitic drugs in ruminants.

Using the benzimidazole and avermectin/milbemycin compounds as model drugs, different in vivo kinetic trials, ex vivo and in vitro biotransformation and drug uptake assays are being performed to characterize the pharmacological behaviour of these drugs in ruminants, and the influence of different factors affecting their clinical efficacy as well as their tissue residue pattern in treated animals. The following type of studies are carried out to generate the pharmacologically-based outcome of the research under development:

-Drug absorption and systemic bioavailavility studies.
-Relative bioavailability and pharmaceutical bioequivalence trials.
-Plasma and target tissue disposition kinetics trials
-Tissue distribution patterns for parent drugs and /or their metabolites
-Tissue residues and milk elimination patterns in treated animals
-Pattern of drug hepatic and extrahepatic biotransformation (in vivo and in vitro studies)
-In vitro drug-parasite interaction assays: enantiomeric metabolism and antimicrotubular activity of benzimidazole anthelmintics.
-Drug uptake/diffusion assays in different helminth parasites under ex vivo conditions.
-Correlation between drug diffusion into target helminth parasites and octanol
-water partition coefficients.
- In vivo and ex vivo evaluations of pharmacokinetic interactions: involvement of drug transporters in the excretion of antiparasitic drugs in laboratory animals and ruminants
- Drug metabolism and drug efflux in target helminth parasites: approaches to understand the resistance mechanisms in to triclabendazole resistant Fasciola hepatica

Prof. Carlos Lanusse (1), Dr Luis Alvarez (2), Dr. Sergio Sanchez Bruni,(3), Dr. Adrián Lifschitz (4), Dra. Laura Moreno Torrejon (5), Lic. en Cs. Farm. Alejandra Pis (6), Dra Fernanda Imperiale (7), Med Vet. Juan Sallovitz (8), Biol. Laura Ceballos (9) Med Vet. Claudia Gonzalez (10) German Moreno- student. (11) Soledad Sazatornil (12)