{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:55:28Z","timestamp":1787885728505,"version":"build-2784847793"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cryptosporidiosis is considered a crucial zoonotic disease caused by widely distributing parasitic protozoa called <jats:italic>Cryptosporidium<\/jats:italic> spp. Nitazoxanide is the only FDA-approved drug but is only effective with a good immune response of the host. In addressing this unmet medical need, we previously identified a compound, namely, LN002, as a potent alternative oxidase inhibitor against cryptosporidiosis. To illustrate the pharmacokinetics, absolute bioavailability, and tissue distribution of LN002 in rats, rapid and sensitive high-performance liquid chromatography was developed and validated for the separation and detection of LN002 in plasma, tissue samples, and intestinal contents. In this study, a single dose of oral administration and intravenous injection of LN002 was used to determine the levels of LN002 in plasma, tissue samples, and intestinal contents by UHLC. Results of the study indicated that after intravenous administration of 1\u00a0mg\/kg LN002, the AUC0\u201324 h, T<jats:sub>1\/2<\/jats:sub>,V<jats:sub>d<\/jats:sub>, and Cl were 7024.86\u00a0h\u00b7ng\/mL, 10.91\u00a0h, 1.69\u00a0L\/kg, and 0.11\u00a0L\/h\/kg, respectively. After oral administration of a single dosage of 100, 200, and 400\u00a0mg\/kg LN002, the T<jats:sub>max<\/jats:sub>, C<jats:sub>max<\/jats:sub>, AUC<jats:sub>0\u201324\u00a0h<\/jats:sub>, T<jats:sub>1\/2<\/jats:sub>, F, V<jats:sub>d<\/jats:sub>, and Cl\/F in plasma of rats were 1\u00a0h, 849.88\u20134033.21\u00a0ng\/mL, 2280.41\u20137498.10\u00a0h\u00b7ng\/mL, 17.96\u201318.83\u00a0h, 0.27%\u20130.32%, 581.54\u2013869.21\u00a0L\/kg, and 25.97\u201339.00\u00a0L\/h\/kg, respectively. After oral administration of 200\u00a0mg\/kg, LN002 was extensively distributed in the main tissues of rats, and massive amounts of LN002 were distributed in the intestine and intestinal contents, indicating its potential as an effective anti-Cryptosporidium compound. After oral administration of a single dosage of 200\u00a0mg\/kg, LN002 has a low bioavailability and high levels in the intestine, which is crucial for the safe and effective treatment of cryptosporidiosis. Overall, the results of this study provide valuable data support for the future study of LN002.<\/jats:p>","DOI":"10.3389\/fphar.2024.1413872","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T04:50:10Z","timestamp":1722315010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics and tissue distribution of LN002, a new compound alternative oxidase inhibitor against Cryptosporidium in rats"],"prefix":"10.3389","volume":"15","author":[{"given":"Minglang","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiguo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenling","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongping","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e4984","DOI":"10.1002\/jms.4984","article-title":"Simple and rapid quantification of ribociclib in rat plasma by protein precipitation and lc-ms\/ms: an application to pharmacokinetics of ribociclib nanoparticles in rats","volume":"58","author":"Alshogran","year":"2023","journal-title":"J. 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