{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T04:36:29Z","timestamp":1759638989887},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,12,21]],"date-time":"2001-12-21T00:00:00Z","timestamp":1008892800000},"content-version":"vor","delay-in-days":124,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2001,8,19]]},"abstract":"<jats:p>Giorgi, M., Salvatori, A. P., Soldani, G., Giusiani, M., Longo, V., Gervasi, P. G., Mengozzi, G. Pharmacokinetics and microsomal oxidation of praziquantel and its effects on the P450 system in three\u2010month\u2010old lambs infested by <jats:italic>Fasciola hepatica. J. vet. Pharmacol. Therap.<\/jats:italic><jats:bold>24,<\/jats:bold> 251\u2013259.<\/jats:p><jats:p>Praziquantel (PZQ) is a broadly effective trematocide and cestocide, widely employed in veterinary and human medicine. In view of several differences in both its pharmacokinetic profile in different animal species and in the cytochrome P450\u2010dependent system between ruminant and nonruminant species, the present study was undertaken to determine the pharmacokinetics of this drug, its effects on the P450 system and the involvement of cytochrome P450 in its metabolism in 3\u2010month\u2010old lambs infested by <jats:italic>Fasciola hepatica<\/jats:italic>. Following both oral and i.m. administration, PZQ disposition was best described by a linear one\u2010compartment open model with a rapid absorption and elimination. Although the PZQ dose used by the i.m. route was only half of that used by the oral route, the mean PZQ plasma concentration was higher after i.m. than after oral treatment. Oral treatment with 30\u2003mg\/kg\/day of PZQ did not modify the mono\u2010oxygenase activities tested, whilst the administration of PZQ at a dose of 60\u2003mg\/kg\/day for 2\u2003days caused a significant decrease in the P450 3A\u2010dependent erythromycin N\u2010demethylase and 6<jats:italic>\u03b2<\/jats:italic> testosterone hydroxylase activities. From the incubation of microsomes from lambs not treated with PZQ, a single metabolite (PZQ 11b\u2010OH or PZQ 1\u2010OH) was identified by GC\/MS analysis. By selective inhibition of the 3A subfamily performed with triacetyloleandromycin, the production of this metabolite declined by about 90% suggesting a prominent role of P450 3A isoforms in this oxidation. These features indicate that agents or drugs which are able to modulate P450 3A\u2010dependent catalysis may interfere with the metabolism, bioavailability and therapeutic effects of PZQ.<\/jats:p>","DOI":"10.1046\/j.1365-2885.2001.00341.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T09:23:19Z","timestamp":1047460999000},"page":"251-259","source":"Crossref","is-referenced-by-count":21,"title":["Pharmacokinetics and microsomal oxidation of praziquantel and its effects on the P450 system in three\u2010month\u2010old lambs infested by <i>Fasciola hepatica<\/i>"],"prefix":"10.1111","volume":"24","author":[{"given":"M.","family":"Giorgi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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