The disposition of pyrantel in the gastrointestinal tract and effect of digesta flow rate on the kinetic behaviour of pyrantel in the pig.

Pigs consuming a diet with slow digesta transit time were orally administered with molar equivalent doses of pyrantel as the citrate and pamoate salt. At appropriate intervals pigs were killed and the quantitative-time distribution of pyrantel throughout the gut contents was determined. Compared with the citrate, there appeared to be greater quantities of the less soluble pamoate salt in the small and large intestine. An additional group of pigs fed on diets with "slow" or "fast" digesta transit time were orally treated with molar equivalent amounts of pyrantel as the citrate and pamoate salt and the respective kinetic disposition of pyrantel in peripheral plasma and quantitative excretion in faeces was determined. The diet type had little effect on pyrantel availability after administration of the less soluble pamoate salt. However, the maximum concentration of pyrantel in plasma was lower and there appeared to be greater quantities of pyrantel retained in the gut and excreted in faeces when the citrate salt was orally administered to pigs fed the "fast" compared to the "slow" diet. Since it is the quantity of pyrantel contained in the gut lumen which is believed to affect efficacy against gastrointestinal parasites, greater efficacy with this anthelmintic should be obtained when pigs are consuming a high fibre diet.

The kinetic disposition of pyrantel citrate and pamoate and their efficacy against pyrantel-resistant Oesophagostomum dentatum in pigs.

The pharmacokinetic disposition of pyrantel after intravenous (i.v.) and oral (p.o.) administration as the citrate and p.o. administration as the pamoate salt was determined in pigs. Following i.v. administration pyrantel was quickly cleared from the bloodstream, exhibiting a terminal half-life of 1.75 +/- 0.19 h and a residence time (MRT) of 2.54 +/- 0.27 h. After p.o. administration as the citrate salt, the absorption time (MAT) of pyrantel was 2.38 +/- 0.25 h and although significant quantities of pyrantel were absorbed (mean bioavailability of 41%) the rapid clearance resulted in a MRT of only 4.92 +/- 0.36 h. By comparison, the significantly extended MAT of the less soluble pamoate salt resulted in reduced circulating concentrations and a significantly lower mean bioavailability of 16%. The poor efficacy of pyrantel citrate against nematodes inhabiting the large intestine of pigs is therefore suggested to result from insufficient quantities of drug passaging to the site of infection. When tested against pyrantel-resistant adult Oesophagostomum dentatum the mean efficacy of pyrantel citrate was only 23%, whereas the efficacy of the lesser absorbed pyrantel pamoate was 75%. These results indicate that for maximum activity pyrantel should be administered to pigs as the pamoate salt.