Evaluation of the pharmacokinetic interaction between ivermectin and albendazole following their combined use in parasitized lambs

ALVAREZ L; LIFSCHITZ, A.; ENTROCASSO, C.; MANAZZA, J.; MOTTIER, L.; BORDA, B.; VIRKEL, G.; LANUSSE, C.

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Año: 2008 vol. 31 p. 230 - 239

0140-7783

  Abstract Mixtures of drugs from different chemical families have been proposed as a valid strategy to delay the development of anthelmintic resistance. The current work summarizes the outcome of the evaluation of the plasma disposition kinetics of albendazole (ABZ) and ivermectin (IVM) administered either alone or co-administered to lambs infected with gastrointestinal (GI) nematodes resistant to both anthelmintic molecules. Thirty six (36) Corriedale lambs naturally infected with multiple resistant GI nematodes were allocated into 6 groups and treated either with ABZ by intravenous (i.v.) injection, IVMIV, ABZIV+ IVMIV, ABZ intraruminal (i.r.), IVM subcutaneous (s.c.), and IVMSC+ABZIR. Plasma samples were collected over 15 days post-treatment and analysed by HPLC. The estimated pharmacokinetic (PK) parameters were statistically compared using parametric and non-parametric statistical tests.  The presence of IVM did not affect the plasma disposition kinetics of ABZ and its metabolites after the i.v. administration. However, the ABZ sulphoxide (ABZSO) area under the concentration vs. time curve (AUC) was significantly lower (P<0.01) after the i.r. administration of ABZ alone compared to that obtained for the combined treatment with IVM (s.c. injection). The IVM plasma AUC obtained after its i.v. co-administration with ABZ was 88 % higher (P< 0.05) compared to the treatment with IVM alone. Any marked difference on IVM PK parameters was observed between the treatments ABZ+IVM and IVM alone injected subcutaneously. The data obtained here indicate that the co-administration of ABZ and IVM does not induce an adverse kinetic interaction. This type of pharmacology based evaluation of drug interactions is becoming highly relevant since drug combinations is now widely used as an alternative to control resistant helminth parasites in livestock.     Key words: Pharmacokinetic interactions, Albendazole, Ivermectin, Anthelmintic resistance.