Safety profile of L-arginine infusion in moderately severe falciparum malaria.

Abstract

BACKGROUND: L-arginine infusion improves endothelial function in malaria but its safety profile has not been described in detail. We assessed clinical symptoms, hemodynamic status and biochemical parameters before and after a single L-arginine infusion in adults with moderately severe malaria. METHODOLOGY AND FINDINGS: In an ascending dose study, adjunctive intravenous L-arginine hydrochloride was infused over 30 minutes in doses of 3 g, 6 g and 12 g to three separate groups of 10 adults hospitalized with moderately severe Plasmodium falciparum malaria in addition to standard quinine therapy. Symptoms, vital signs and selected biochemical measurements were assessed before, during, and for 24 hours after infusion. No new or worsening symptoms developed apart from mild discomfort at the intravenous cannula site in two patients. There was a dose-response relationship between increasing mg/kg dose and the maximum decrease in systolic (rho = 0.463; Spearman's, p = 0.02) and diastolic blood pressure (r = 0.42; Pearson's, p = 0.02), and with the maximum increment in blood potassium (r = 0.70, p<0.001) and maximum decrement in bicarbonate concentrations (r = 0.53, p = 0.003) and pH (r = 0.48, p = 0.007). At the highest dose (12 g), changes in blood pressure and electrolytes were not clinically significant, with a mean maximum decrease in mean arterial blood pressure of 6 mmHg (range: 0-11; p<0.001), mean maximal increase in potassium of 0.5 mmol/L (range 0.2-0.7 mmol/L; p<0.001), and mean maximal decrease in bicarbonate of 3 mEq/L (range 1-7; p<0.01) without a significant change in pH. There was no significant dose-response relationship with blood phosphate, lactate, anion gap and glucose concentrations. All patients had an uncomplicated clinical recovery. CONCLUSIONS/SIGNIFICANCE: Infusion of up to 12 g of intravenous L-arginine hydrochloride over 30 minutes is well tolerated in adults with moderately severe malaria, with no clinically important changes in hemodynamic or biochemical status. Trials of adjunctive L-arginine can be extended to phase 2 studies in severe malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00147368.

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10.1371/journal.pone.0002347

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Yeo, Tsin W, Daniel A Lampah, Retno Gitawati, Emiliana Tjitra, Enny Kenangalem, Donald L Granger, J Brice Weinberg, Bert K Lopansri, et al. (2008). Safety profile of L-arginine infusion in moderately severe falciparum malaria. PLoS One, 3(6). p. e2347. 10.1371/journal.pone.0002347 Retrieved from https://hdl.handle.net/10161/4494.

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Weinberg

Joe Brice Weinberg

Professor Emeritus of Medicine

Dr. Weinberg is a board-certified hematologist and medical oncologist who serves as Professor of Medicine and Immunology and Associate Professor of Obstetrics and Gynecology at the Duke University Medical Center, and staff physician in hematology-oncology at the Durham V.A. Medical Center. His clinical interests are in hematology and oncology, and his research focuses on blood cells, nitric oxide (NO), and leukemia. The work includes studies of resistance to infection, pathways of inflammation, and regulation of normal and leukemic cell life and death. His current work includes studies of leukemia (primarily chronic lymphocytic leukemia); the roles of NO and arginine in the resistance to malaria; and the interactions of NO, prostaglandins, and mechanical force in inflammation and arthritis.


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