{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:21:52Z","timestamp":1789082512068,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Science Program"},{"name":"Global Health Institute, Merck Serono"},{"name":"African Institute of Biomedical Science and Technology"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Racemic praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis. R\u2010Praziquantel (R\u2010PZQ) has been shown as the therapeutic form, whereas S\u2010PZQ is less efficacious and responsible for the bitter taste of the tablet. This study aimed at investigating the metabolism of R\u2010 and S\u2010PZQ as this could have implications on efficacy and safety of racemate and R\u2010PZQ specific formulations under development. In vitro CYP reaction phenotyping assay using 10 recombinant CYP (rCYP) isoenzymes showed hepatic CYP1A2, 2C19, 2D6, 3A4, and 3A5 were the major enzymes involved in metabolism of PZQ. Enzyme kinetic studies were performed by substrate depletion and metabolite formation methods, by incubating PZQ and its R\u2010 or S\u2010enantiomers in human liver microsomes (HLM) and the rCYP enzymes. The effect of selective CYP inhibitors on PZQ metabolism was assessed in HLM. CYP1A2, 2C19, and 3A4 exhibited different catalytic activity toward PZQ, R\u2010 and S\u2010enantiomers. Metabolism of R\u2010PZQ was mainly catalyzed by CYP1A2 and CYP2C19, whereas metabolism of S\u2010PZQ was mainly by CYP2C19 and CYP3A4. Based on metabolic CL\n                    <jats:sub>int<\/jats:sub>\n                    obtained through formation of hydroxylated metabolites, CYP3A4 was estimated to contribute 89.88% to metabolism of S\u2010PZQ using SIMCYP\n                    <jats:sup>\u00ae<\/jats:sup>\n                    IVIVE prediction. Reanalysis of samples from a human PZQ\u2010ketoconazole (KTZ) drug\u2010drug interaction pharmacokinetic study confirmed these findings in that KTZ, a potent inhibitor of CYP3A, selectively increased area under the curve of S\u2010PZQ by 68% and that of R\u2010PZQ by just 9%. Knowledge of enantioselective metabolism will enable better understanding of variable efficacy of PZQ in patients and the R\u2010PZQ formulation under development.\n                  <\/jats:p>","DOI":"10.1002\/prp2.618","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T06:57:44Z","timestamp":1595487464000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["In vitro and in vivo human metabolism and pharmacokinetics of S\u2010 and R\u2010praziquantel"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-8753","authenticated-orcid":false,"given":"Nyasha Nicole","family":"Kapungu","sequence":"first","affiliation":[{"name":"African Institute of Biomedical Science and Technology (AiBST) Harare Zimbabwe"},{"name":"Department of Clinical Pharmacology University of Zimbabwe (UZ) Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4751-9726","authenticated-orcid":false,"given":"Xueqing","family":"Li","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&amp;D AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Nhachi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Zimbabwe (UZ) Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-4151","authenticated-orcid":false,"given":"Collen","family":"Masimirembwa","sequence":"additional","affiliation":[{"name":"African Institute of Biomedical Science and Technology (AiBST) Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-6609","authenticated-orcid":false,"given":"Roslyn Stella","family":"Thelingwani","sequence":"additional","affiliation":[{"name":"African Institute of Biomedical Science and Technology (AiBST) Harare Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0467"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4172\/2329-9088.1000135"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjid.2014.11.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed4010040"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-017-2293-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S98096"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00227-16"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02741-14"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0731-7085(01)00417-4"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-003-0636-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.05.001"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00560463"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03189418"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2005.01.033"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.2610030204"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1256"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.5.1614-1616.2002"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-002-0751-z"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-019-02663-8"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.129319"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.37.9.1561"},{"key":"e_1_2_10_23_1","unstructured":"BairdJ BeggC PritchardMP VoiceMW.Effects of common organic solvents on the activity of recombinant human cytochrome P450s expressed inE coli. 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