Comparative plasma exposure of albendazole after administration of rapidly disintegrating tablets in dogs.

CASTRO, S; DIB, A; SUAREZ, G; ALLEMANDI, D; LANUSSE, C; SANCHEZ BRUNI, S; PALMA, S

BioMed Research International

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2013 p. 1 - 7

2314-6133

Benzimidazoles (BZD) form a family of related anthelmintic compounds and their metabolites/derivatives, which are widely used in antiparasite therapy in both veterinary and human medicine. The parent drugs, febendazole (FBZ) and albendazole (ABZ), contain a sulphur atom as a sulphide at position 5 of the BZD molecule. These sulphides are subjected, mainly in the liver, to phase I reactions (oxidation), catalysed by the flavin monooxygenase (FMO) and the cytochrome P-450 (Cyt P-450) enzyme systems to form sulfoxide (SO) metabolites, with FBZSO (oxfendazole; OFZ) and ABZSO being the primary, pharmacologically active metabolites generated [1, 2]. In a second metabolic reaction (sulphonation), catalysed by the Cyt P-450 system OFZ and ABZSO are transformed into inactive sulphone (SO2) metabolites, namely, FBZSO2 and ABZSO2, respectively [2]. Several studies have suggested that only limited rates of dissolution and absorption of BZD anthelmintics are achieved in cat, dog, and human. Consequently, these compounds may need to be given at higher doses or as multiple administrations in order to provide adequate therapeutic concentrations to give an acceptable anthelmintic efficacy [3? 5].Therefore, new pharmaceutical alternatives are necessary for increasing the BZD drug exposure to shorten themultiple administrations. According to the biopharmaceutical classification system (BCS), ABZ is a BCS class II compound [6] with an aqueous solubility of less than 5 𝜇g/mL and many investigations have suggested that dissolution of ABZ is the rate-limiting step for its absorption [7]. It is thus desirable to enhance the dissolution rate of the drug in order to increase its rate of absorption. The rate at which a solid dissolves is directly proportional to the surface area of drug exposed to the dissolution medium and is given by the Noyes-Whitney equation [8]. Solid dispersions (SDs), which are defined as molecular mixtures of poor water-soluble drugs and hydrophilic carriers, have been proposed as alternatives for improving the dissolution rate of these kinds of drugs [9], with ABZ dissolution having previously been assayed at our laboratory using solid dispersions (SDs) with poloxamer 188 (P 188) as carrier. Although the proportion of P 188 incorporated in SDs had a marked influence on ABZ release during the initial