Albendazole is a member of the benzimidazole group of anthelmintics with broad-spectrum activity against gastro-intestinal roundworms including inhibited larval stages, tapeworms, liver flukes and lungworms in many species. In the ruminant animal the rumen acts as a “reservoir” of undissolved albendazole and rhe slow passage of drug through the rumen serves to maintain concentrations of albendazole or active metabolic products in the more distal parts of the gastro-intestinal tract and in the systemic compartment over a number of days. Ruminal by-pass via the oesophageal (reticular) groove could lead to inferior activity of albendazole. In a previous report on albendazole pharmacokinetics we found little evidence of subsitantial ruminal by-pass with albendazole given orally as a drench (suspension) although small amounts passed (directly to the abomasum in individual sheep.
In this communication we report on the concentrations of albendazole and its major metabolites (albendazole sulfoxide and albendazole sulfone) in ruminal and abomasal fluid after oral administration of albendazole as a paste formulation and compare these with those found after oral administration of the drench (suspension) formulation. Paste formulations are a preferred method of treatment in many countries and this work was necessary to assess whether efficacy and other ldara obtained using the drench formulation (favoured in the U. K. and U.S.A.) is applicable also to the paste formulation. It is of value to consider the concentrations of parent drug and metabolites in both the gastro-intestinal tract and plasma, since albendazole is used for the control of both systemic (lungworm, liver fluke) and gastro-intestinal parasites.
Material and Methods
Three sheep (Finn-Dorset) about one year old were used. They were fitted with permanent ruminal and abomasal cannulae introduced more than two months before the commencement of the trial. The same three sheep (B, S, G) were used for both the paste and the suspension trial. The suspension trial was carried out two months prior to the paste trial and the weights of the sheep were 34.0, 25.0, 19.5 kg. (suspension) and 40.3, 24.7, 22.5 kg. (paste), respectively, at the start of the two trials. The animals were kept indoors on a hay and concentrate diet throughout.
Albendazole was administered at a dose rate of 10mg./kg. in both the paste and suspension experiments. Both paste and suspension were placed on the back of the tongue of each sheep from a syringe. The suspension was a commercial formulation (“Valbazen” 2.5% w/v,) and the paste (Lot No. 12/78 KO3; 30% w/v).
Samples for Analysis
Plasma, rumen fluid and abomasal fluid were collected before and at intervals after drug administration. Rumen fluid and abomasal fluid were centrifuge at 1,000 g. for 10min and the supernatant was carefully removed and filtered hrough Whatman No. I filter paper. The concentrations reported here represent dissolved (and therefore biologically active) benzimidazole; undissolved drug was removed by centrifugation.
Method of Analysis
Analysis of albendazole was made by High Performance Liquid Chromatography using a sensitive and specifi method reported by us. The principal metabolites (sulfoxide and ,sulfone) have similar retention times in the solvent system used for albendazole determination (Solvent-Methanol: Ammonium Carbonate [0.05 M] 75 : 25. Retention times – Albendazole 4.3 min, Sulfoxide and Sulfone 2.4 min) and therefore a different solvent system (Merhanol : Water 80 : 20 + 1 μL. perchloric acid [1.l% w/v] per ml.) of solvent was used for the separation and quantitation of sulfoxide and sulfone. Under these conditions sulfone and sulfoxicde have retention times of 2.9 min and 4.6 min, respectively. The total sulfoxide anid sulfone concentrations obtained in the methanol : ammonium carbonate system provided an additional check of total metabolite concentrations. Albendazole sulfoxide was synthesized by us and identified by infra-red spectroscopy and other techniques.
S. E. MARRINE, Zbl. Vet. Med. B, 28, 19-26 (1981)