{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:14:56Z","timestamp":1790262896514,"version":"4.1.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The tolerability, safety, and disposition of dihydroartemisinin (DHA) and piperaquine (PQ) were assessed in 32 pregnant (second\/third trimester) and 33 nonpregnant Papua New Guinean women randomized to adult treatment courses of DHA-PQ (three daily doses) or sulfadoxine-pyrimethamine (SP)-PQ (three daily PQ doses, single dose of SP). All dose adminstrations were observed, and subjects fasted for 2 h postdose. Plasma PQ was assayed by using high-performance liquid chromatography, and DHA was assessed by using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models were developed using a population-based approach. Both regimens were well tolerated. There was an expected increase in the rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment. Two pregnant and two nonpregnant women had\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            parasitemia which cleared within 48 h, and no other subject became slide positive for malaria during 42 days of follow-up. Of 30 pregnant women followed to delivery, 27 (90%) delivered healthy babies and 3 (10%) had stillbirths; these obstetric outcomes are consistent with those in the general population. The area under the plasma PQ concentration-time curve (AUC\n            <jats:sub>0\u2013\u221e<\/jats:sub>\n            ) was lower in the pregnant patients (median [interquartile range], 23,721 \u03bcg \u00b7 h\/liter [21,481 to 27,951 \u03bcg \u00b7 h\/liter] versus 35,644 \u03bcg \u00b7 h\/liter [29,546 to 39,541 \u03bcg \u00b7 h\/liter];\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001) in association with a greater clearance relative to bioavailability (73.5 liters\/h [69.4 to 78.4] versus 53.8 liters\/h [49.7 to 58.2];\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001), but pregnancy did not influence the pharmacokinetics of DHA. The apparent pharmacokinetic differences between the present study and results from other studies of women with uncomplicated malaria that showed no effect of pregnancy on the AUC\n            <jats:sub>0\u2013\u221e<\/jats:sub>\n            of PQ and greater bioavailability may reflect differences in postdose fat intake, proportions of women with malaria, and\/or racial differences in drug disposition.\n          <\/jats:p>","DOI":"10.1128\/aac.00326-15","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T02:32:06Z","timestamp":1431397926000},"page":"4260-4271","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Population Pharmacokinetics, Tolerability, and Safety of Dihydroartemisinin-Piperaquine and Sulfadoxine-Pyrimethamine-Piperaquine in Pregnant and Nonpregnant Papua New Guinean Women"],"prefix":"10.1128","volume":"59","author":[{"given":"John M.","family":"Benjamin","sequence":"first","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brioni R.","family":"Moore","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea"},{"name":"School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Salman","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Page-Sharp","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Curtin University of Technology, Bentley, Western Australia, Australia"},{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somoyang","family":"Tawat","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gumal","family":"Yadi","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Lorry","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Siba","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia"},{"name":"Department of Microbiology, Division of Veterinary and Biomedical Sciences, James Cook University, Townsville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin T.","family":"Batty","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Curtin University of Technology, Bentley, Western Australia, Australia"},{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne J.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea"},{"name":"Infection and Immunity, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Veterinary and Biomedical Sciences, James Cook University, Townsville, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Victoria, Australia"},{"name":"Center de Recerca en Salut Internacional de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M. 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