{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:30:17Z","timestamp":1758709817315},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T00:00:00Z","timestamp":1448409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T00:00:00Z","timestamp":1448409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99\u2013411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS\/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99\u2013411 and of piperaquine and 99\u2013411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99\u2013411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99\u2013411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99\u2013411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99\u2013411, an <jats:italic>in situ<\/jats:italic> permeability study was performed by co-perfusing lumefantrine and 99\u2013411. In presence of lumefantrine, the absorption of 99\u2013411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99\u2013411 when tested <jats:italic>in vitro<\/jats:italic> in human liver microsomes. Additionally, ATPase assay suggest that 99\u2013411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well.<\/jats:p>","DOI":"10.1038\/srep17264","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T10:11:12Z","timestamp":1448446272000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessment of pharmacokinetic compatibility of short acting CDRI candidate trioxane derivative, 99\u2013411, with long acting prescription antimalarials, lumefantrine and piperaquine"],"prefix":"10.1038","volume":"5","author":[{"given":"Isha","family":"Taneja","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanumuri Siva Rama","family":"Raju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheelendra Pratap","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Wahajuddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,11,25]]},"reference":[{"key":"BFsrep17264_CR1","unstructured":"WHO World malaria report 2013, World Health Organization, 2014."},{"key":"BFsrep17264_CR2","doi-asserted-by":"publisher","first-page":"P19","DOI":"10.1186\/1475-2875-13-S1-P19","volume":"13","author":"MT Bretscher","year":"2014","unstructured":"Bretscher, M. T. et al. A comparison of the duration of post-treatment protection of artemether-lumefantrine, dihydroartemisinin-piperaquine and artesunate-amodiaquine for the treatment of uncomplicated malaria. Malar. J. 13, P19 (2014).","journal-title":"Malar. J."},{"key":"BFsrep17264_CR3","doi-asserted-by":"publisher","first-page":"e95681","DOI":"10.1371\/journal.pone.0095681","volume":"9","author":"J Pfeil","year":"2014","unstructured":"Pfeil, J., Borrmann, S. & Tozan, Y. Dihydroartemisinin-piperaquine vs. artemether-lumefantrine for first-line treatment of uncomplicated malaria in African children: a cost-effectiveness analysis. PLoS One. 9, e95681 (2014).","journal-title":"PLoS One."},{"key":"BFsrep17264_CR4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1128\/AAC.04181-14","volume":"59","author":"MM Plucinski","year":"2015","unstructured":"Plucinski, M. M. et al. 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