Albendazole sulphoxide enantiomeric ratios in plasma and target tissues after intravenous administration of ricobendazole to cattle

Abstract

The comparative concentration profiles of the (+) and (-) albendazole sulphoxide (ABZSO) enantiomers obtained in plasma and in selected target tissues/fluids after intravenous (i.v.) administration of a racemic formulation of ricobendazole (RBZ) to cattle were characterised. Fourteen Holstein calves received RBZ (racemic solution, 150 mg/mL) by i.v. administration at 7.5 mg/kg. Jugular blood samples were collected over 48 h post-treatment (plasma kinetic trial) and two animals were sacrificed at either 4, 12, 20, 28 or 32 h post-treatment to obtain samples of abomasal/small intestine mucosal tissue, abomasal/small intestine fluids, bile, liver and lung tissue (tissue distribution study). The (-)ABZSO enantiomer was depleted significantly faster from plasma compared with the (+)ABZSO antipode. The plasma AUC for (+)ABZSO (38.3 microg. h/mL) was significantly higher (P < 0.05) compared with that obtained for (-)ABZSO (20.5 microg. h/mL). The (+)ABZSO enantiomer was the predominant antipode measured in bile, abomasal fluid and abomasal mucosa. For instance, at 12 h post-treatment the (+)/(-) concentration ratios were: 12.9 (plasma), 1.62 (abomasal mucosa), 13.0 (abomasal fluid), 2.92 (intestinal mucosa), 9.87 (intestinal fluid) and 21.5 (bile). No marked differences between the concentration profiles of both enantiomers were observed in the liver tissue. Albendazole (ABZ) was recovered from the liver, lung and gastrointestinal (GI) mucosal tissues of RBZ-treated calves up to 32 h post-treatment, probably produced by a GI microflora-mediated sulphoreduction of RBZ. An enantioselective kinetic behaviour may account both for the faster depletion of the (-) enantiomer and for the higher availabilities of the (+) antipode observed in plasma and in most of the tissues/fluids investigated. The simultaneous evaluation of the plasma kinetics and tissue concentration profiles of both enantiomeric forms reported here, may help to interpret the relationship between chiral behaviour and pharmacological action for sulphoxide derivatives of benzimidazole (BZD) methylcarbamate anthelmintics.

Comparative Hepatic and Extrahepatic Enantioselective Sulfoxidation of Albendazole and Fenbendazole in Sheep and Cattle

“…Large quantities of ABZ were recovered from tissues of parasite location such as lung parenchyma and small intestinal mucosa in both sheep and cattle Cristofol et al, 2001). FBZ has been recovered in both target tissues following oral administration of OFZ to cattle (G. Virkel, L. Mottier, and C. Lanusse, unpublished observations).…”

“…The (ϩ) ABZSO enantiomer predominates in plasma (Delatour et al, 1991;Cristofol et al, 2001) and in tissues of parasite location such as lung and GI mucosa (Cristofol et al, 2001), as well as in a target parasite such as the liver fluke Fasciola hepatica . For example, the (ϩ) ABZSO enantiomer represents 91% of the total ABZSO plasma area under the concentration versus time curve (AUC) in cattle and 86% in sheep (Delatour et al, 1991).…”

“…Thus, two ABZSO and OFZ enantiomers have been identified (by chiral separation) in the plasma of sheep after administration of ABZ, FBZ (prochiral molecules) (Delatour et al, 1990), and OFZ (Sánchez et al, 2002). It has been shown that (ϩ) ABZSO is the main enantiomeric form recovered in plasma (Delatour et al, 1991) and in tissues of parasite location following ABZ treatment to sheep and ABZSO administration to cattle (Cristofol et al, 2001). Similarly, (ϩ) OFZ prevails in the systemic circulation after both FBZ (Delatour et al, 1990) and OFZ (Sánchez et al, 2002) administration to sheep.…”

Effect of amphiphilic surfactant agents on the gastrointestinal absorption of albendazole in cattle

“…Moreover, the absorbed drug is more important for the efficacy against GI nematodes than unabsorbed drug passing down the GI tract [21]. Thus, the plasma concentration profiles of anthelmintically active BZD moieties reflect the pattern of exposure of worms in the GI tract (mucosas or lumen) as well in other tissues of parasite location such as liver or lung [20,22,23]. It has been recently shown that plasma profiles of ABZ metabolites correlate with those obtained in different tissues/fluids and in target parasites (Moniezia spp., Haemonchus spp.…”

Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics

“…1 Recently, pharmacokinetic studies have been published using an injectable form of the active sulphoxide metabolite of ABZ and the benefits of injectable forms of benzimidazoles have been discussed. [3][4][5][6] Ricobendazole (RBZ) or albendazole sulphoxide (Scheme 1) is reported as the active metabolite of ABZ. 1,[7][8][9] Following oral administration of ABZ 8,10 in sheep or its prodrug netobimin in cattle, 11 ABZ concentrations are either very low (0.05 mg/mL) or not detected in the plasma and systemic activity is attributed to the active sulphoxide metabolite.…”