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.) a nd oral (p.o.) administration as the citrate and p.o. administration a s the pamoate salt was determined in pigs. Following i.v. administrati on pyrantel was quickly cleared from the bloodstream, exhibiting a ter minal 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 absorpt ion time (MAT) of pyrantel was 2.38 +/- 0.25 h and although significan t quantities of pyrantel were absorbed (mean bioavailability of 41%) t he rapid clearance resulted in a MRT of only 4.92 +/- 0.36 h. By compa rison, the significantly extended MAT of the less soluble pamoate salt resulted in reduced circulating concentrations and a significantly lo wer 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 O esophagostomum 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. Copyright (C) 1996 Austr alian Society for Parasitology. Published by Elsevier Science Ltd.