{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:23:13Z","timestamp":1754162593881,"version":"3.41.2"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>Introduction<\/jats:title>\n            <jats:p>Praziquantel (PZQ) is commonly used to treat schistosomiasis; however, there is considerable interindividual variability in its efficacy, partly because of genetic variation. Data on this relationship is scarce across Africa \u2013 where schistosomiasis is prevalent. This study aimed to investigate the pharmacokinetic\/pharmacodynamic and pharmacogenetic relationship between PZQ and its metabolites in a Zimbabwean population infected with <jats:italic toggle=\"yes\">Schistosoma haematobium<\/jats:italic> by leveraging dried blood spots (DBS) and mass spectrometry (MS).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>DBS were obtained from 38 Zimbabwean participants on PZQ treatment at four-time points (0.5, 1.5, 2.5, and 4\u2005h). We compared two extraction methods for recovering PZQ and its metabolites from the DBS cards and performed MS analysis to determine the concentrations. A random forest model was used to determine whether <jats:italic toggle=\"yes\">CYP1A2<\/jats:italic>, <jats:italic toggle=\"yes\">CYP2C9<\/jats:italic>, <jats:italic toggle=\"yes\">CYP2C19<\/jats:italic>, <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>, <jats:italic toggle=\"yes\">CYP3A4<\/jats:italic>, and <jats:italic toggle=\"yes\">CYP3A5<\/jats:italic> known variants were predictive of PZQ efficacy. The relationships between PZQ\/metabolite concentration, metabolite ratio, and drug exposure with genotype were determined using a one-way analysis of variance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>An acetonitrile and water (4\u2005:\u20051) mixture was determined to be optimal for recovering PZQ and its metabolites from the DBS cards. Subsequent MS analysis identified PZQ and six metabolite compounds \u2013 including phase 1 metabolites (\u20132H)-O-PZQ, O2-PZQ, and 4-OH-PZQ. Pooled MS sampling was comparable to individual MS sampling for determining pharmacokinetic profiles at the 2.5 and 4-h time points. The (\u20132H)-O-PZQ and O2-PZQ metabolites had significantly higher concentrations in participants with <jats:italic toggle=\"yes\">CYP2C9*1\/*9<\/jats:italic> and <jats:italic toggle=\"yes\">*9\/*9<\/jats:italic> versus those with <jats:italic toggle=\"yes\">CYP2C9*1\/*1. CYP1A2<\/jats:italic> rs2069514-A (formerly <jats:italic toggle=\"yes\">*1C<\/jats:italic>) and rs762551-A (<jats:italic toggle=\"yes\">CYP1A2*30<\/jats:italic>; formerly <jats:italic toggle=\"yes\">*1F<\/jats:italic>) were observed to alter PZQ pharmacokinetic profiles; however, differences in analyte concentrations across the corresponding genotypes were NS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We show that low-cost microsampling using DBS and MS is feasible for detecting and quantifying PZQ and its metabolites. Furthermore, our pharmacogenetics analysis elucidates the impact of known cytochrome P450 variants on PZQ drug response in an African setting.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000572","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T08:02:07Z","timestamp":1749801727000},"page":"197-213","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Microsampling with dried blood spots and mass spectrometry enables PK\/PD profiling of responses to praziquantel in a Schistosoma haematobium\u2013exposed Zimbabwean population"],"prefix":"10.1097","volume":"35","author":[{"given":"David","family":"Twesigomwe","sequence":"first","affiliation":[{"name":"Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"},{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Zdesenko","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research"},{"name":"Tackling Infections to Benefit Africa (TIBA) Partnership, TIBA Global Health Research Unit, Ashworth Laboratories, University of Edinburgh, King\u2019s Buildings, Edinburgh, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafira","family":"Mduluza","sequence":"additional","affiliation":[{"name":"TIBA Zimbabwe, Biochemistry Department, Centre for Immunology and Infection Research, University of Zimbabwe, Harare, Zimbabwe"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Blackburn","sequence":"additional","affiliation":[{"name":"MVLS Shared Research Facilities, Joseph Black Building, Glasgow University, Gilmorehill Campus, University Place"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Burchmore","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Mutapi","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research"},{"name":"Tackling Infections to Benefit Africa (TIBA) Partnership, TIBA Global Health Research Unit, Ashworth Laboratories, University of Edinburgh, King\u2019s Buildings, Edinburgh, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"year":"2023","key":"R1-20250730","article-title":"Schistosomiasis."},{"key":"R2-20250730","doi-asserted-by":"crossref","first-page":"e0008388","DOI":"10.1371\/journal.pntd.0008388","article-title":"Six rounds of annual praziquantel treatment during a National Helminth Control Program significantly reduced schistosome infection and morbidity levels in a cohort of school children in Zimbabwe.","volume":"14","author":"Mduluza","year":"2020","journal-title":"PLoS NeglTrop Dis"},{"key":"R3-20250730","doi-asserted-by":"crossref","first-page":"e0008649","DOI":"10.1371\/journal.pntd.0008649","article-title":"Drug metabolism and pharmacokinetics of praziquantel: a review of variable drug exposure during schistosomiasis treatment in human hosts and experimental models.","volume":"14","author":"Zdesenko","year":"2020","journal-title":"PLoS NeglTrop Dis"},{"key":"R4-20250730","doi-asserted-by":"crossref","first-page":"e07275","DOI":"10.1016\/j.heliyon.2021.e07275","article-title":"Analysis of tamoxifen and its metabolites in dried blood spot and volumetric absorptive microsampling: comparison and clinical application.","volume":"7","author":"Maggadani","year":"2021","journal-title":"Heliyon"},{"key":"R5-20250730","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3390\/pharmaceutics12090809","article-title":"Barriers to implementing clinical pharmacogenetics testing in sub-Saharan Africa. 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