Gastrointestinal distribution of albendazole metabolites following netobimin administration to cattle: relationship with plasma disposition kinetics

Abstract

The gastrointestinal (GI) distribution and plasma disposition kinetics of albendazole (ABZ) metabolites after oral administration of netobimin (NTB) to cattle were studied. Eight Holstein steers (150-180 kg) were surgically fitted with permanent cannulae in the rumen, abomasum and ileum. After post-surgical recovery, the animals were treated orally with a suspension of netobimin zwitterion (400 mg/ml) at 20 mg/kg. Jugular blood and ruminal, abomasal and ileal fluid samples were taken serially over a 96 h period and analysed by HPLC for NTB and its metabolites, including ABZ, ABZ sulphoxide (ABZSO), ABZ sulphone (ABZSO2) and amino-albendazole sulphone (NH2ABZSO2). NTB parent drug was only found in the GI tract and for only 12-18 h post-treatment. ABZSO and ABZSO2 were the main metabolites found in plasma, being present for 30-36 h. These metabolites were exchanged between plasma and different GI fluids and were greatly concentrated in the abomasum. This phenomenon may account for the presence of ABZ, ABZSO and ABZSO2 in the GI tract for 72 h post-treatment despite the fact that ABZ was not detected in plasma and ABZSO and ABZSO2 were detected for only 30-36 h in plasma. The presence of ABZ and ABZSO in the abomasum and intestine for this extended period of time is probably relevant for anthelmintic efficacy against GI parasites. The NH2 ABZSO2 metabolite was detected in plasma, abomasum and ileum and its disposition kinetics were characterized for the first time.

Influence of diet on the pattern of gastrointestinal biotransformation of netobimin and albendazole sulphoxide in sheep

“…Both metabolites are reversibly exchanged between plasma and the GI tract in a pH gradient-mediated distribution process (21). This pH gradient facilitates the concentration of ABZSO in all GI compartments including the rumen.…”

Comparative disposition of ricobendazole enantiomers after intravenous and subcutaneous administration of a racemic formulation to calves

“…It has been shown that plasma concentration profiles of anthelmintic compounds reflect the pattern of exposure of worms in the digestive tract as well as in other tissues [17,18]. BZD anthelmintics are reversibly exchanged between plasma and Figure 4.…”

“…BZD anthelmintics are reversibly exchanged between plasma and Figure 4. Evolution of the RBZ enantiomeric proportions after iv (left) and sc (right) administration of a racemic dose (7.5 mg/kg) of RBZ to cattle gastrointestinal tract in a pH gradient-mediated distribution process [17]. RBZ is a weak base (pK a 7.8); at plasma pH there will be a higher proportion of this molecule in the lipophilic nonionic form, which facilitates its passive diffusion from plasma to different tissues including the digestive tract.…”

“…The peak concentration (C max ) and time to peak concentration (T max ) were read from the plotted concentration-time curve of each analyte. The area under the concentration -time curves (AUC) was calculated by the trapezoidal rule [17], and further extrapolated to infinity by dividing the last experimental plasma concentration by the terminal slope (i). The systemic bioavailability (F) obtained after the sc treatment was estimated as AUC sc / AUC iv .…”

Albendazole Solid Dispersions: Influence of Dissolution Medium Composition on In Vitro Drug Release

“…The unsatisfactory ABZ dissolution rate limits its absorption; therefore, it is poorly and erratically absorbed from the gastrointestinal tract. In vivo studies (17,18) have demonstrated that the oral absorption of benzimidazole compounds depends on their dissolution at low pH and is closely related to the rate of gastric emptying and gut transit time. The USP indicates that the dissolution medium used to evaluate ABZ dissolution is 0.1 N HCl (19).…”