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The World Health Organization (WHO) recommends adding a single low dose of primaquine to the standard artemisinin-based combination therapy (ACT) in order to block malaria transmission in regions with low malaria transmission. However, the haemolytic toxicity is a major adverse outcome of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects. This study aimed to characterize the pharmacokinetic properties of primaquine and its major metabolites in G6PD-deficient subjects.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A single low-dose of primaquine (0.4\u20130.5\u00a0mg\/kg) was administered in twenty-eight African males. Venous and capillary plasma were sampled up to 24\u00a0h after the drug administration. Haemoglobin levels were observed up to 28\u00a0days after drug administration. Only PQ, carboxy-primaquine (CPQ), and primaquine carbamoyl-glucuronide (PQCG) were present in plasma samples and measured using liquid chromatography mass spectrometry. Drug and metabolites\u2019 pharmacokinetic properties were investigated using nonlinear mixed-effects modelling.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Population pharmacokinetic properties of PQ, CPQ, and PQCG can be described by one-compartment disposition kinetics with a transit-absorption model. Body weight was implemented as an allometric function on the clearance and volume parameters for all compounds. None of the covariates significantly affected the pharmacokinetic parameters. No significant correlations were detected between the exposures of the measured compounds and the change in haemoglobin or methaemoglobin levels. There was no significant haemoglobin drop in the G6PD-deficient patients after administration of a single low dose of PQ.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>A single low-dose of PQ was haematologically safe in this population of G6PD-normal and G6PD-deficient African males without malaria.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> NCT02535767<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-024-04979-y","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T11:01:59Z","timestamp":1716289319000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetics of primaquine and its metabolites in African males"],"prefix":"10.1186","volume":"23","clinical-trial-number":[{"clinical-trial-number":"nct02535767","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Palang","family":"Chotsiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almahamoudou","family":"Mahamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halimatou","family":"Diawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pius S.","family":"Fasinu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalifa","family":"Diarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koualy","family":"Sanogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun","family":"Bousema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry A.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alassane","family":"Dicko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roly","family":"Gosling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"4979_CR1","volume-title":"Guidelines for the treatment of malaria","author":"WHO","year":"2015","unstructured":"WHO. 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It also underwent human subjects review at the US Centers for Disease Control and Prevention and approved as non-engagement in human subject research. The trial was registered at ClinicalTrials.gov (registration no. NCT02535767).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The confidentiality of the participants\u2019 records has been observed according to ethical regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"159"}}