Intravenous Ibuprofen (IV-ibuprofen) Controls Fever Effectively in Adults with Acute Uncomplicated Plasmodium falciparum Malaria but Prolongs Parasitemia

Srivicha Krudsood Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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Noppadon Tangpukdee Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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Polrat Wilairatana Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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Nantaporn Pothipak Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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Chatnapa Duangdee Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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David A. Warrell Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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Sornchai Looareesuwan Department of Tropical Hygiene, Department of Clinical Tropical Medicine, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom

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Because some febrile patients are unable to swallow or retain oral antipyretic drugs, we carried out a double-blind, placebo-controlled trial in which intravenous ibuprofen (IV-ibuprofen) was given to adults hospitalized with fever associated with acute uncomplicated falciparum malaria treated with oral artesunate plus mefloquine. Thirty patients received IV-ibuprofen 400 mg and 30 received placebo every 6 hours for 72 hours. Reduction in the area above 37.0°C versus time curve was significantly greater for IV-ibuprofen than for placebo during the first 72 hours after first administration. No patients developed severe malaria; parasite clearance was delayed in the patients whose fevers were controlled by IV-ibuprofen (median 37.3 hours versus 23.7 hours in the placebo group [P = 0.0024]). This difference did not appear to be clinically important Adverse events, none considered severe, occurred equally in both groups. IV-ibuprofen was effective and well tolerated in reducing fever in febrile inpatients with malaria.

Author Notes

*Address correspondence to David A. Warrell, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. E-mail: david.warrell@ndm.ox.ac.uk
†Deceased.

Financial support: This study and its report were supported by Cumberland Pharmaceuticals Inc. (Nashville, TN), which had a role in the study design, data acquisition, statistical analyses, and the decision to publish the findings. However, the authors had complete access to all study data and autonomy as to the report's final content.

Disclosure: DAW's visits to the study site were sponsored by Cumberland Pharmaceuticals.

Authors' addresses: Srivicha Krudsood, Department of Tropical Hygiene, Mahidol University, Bangkok, Thailand. Noppadon Tangpukdee and Polrat Wilairatana, Department of Clinical Tropical Medicine, Mahidol University, Bangkok, Thailand. Nantaporn Pothipak and Chatnapa Duangdee, Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. David A. Warrell, Nuffield Department of Clinical Medicine, University of Oxford, UK.

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