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.
Type
Journal articleSubject
AdultArginine
Blood Glucose
Blood Pressure
Dose-Response Relationship, Drug
Electrolytes
Humans
Hydrogen-Ion Concentration
Infusions, Intravenous
Malaria, Falciparum
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https://hdl.handle.net/10161/4494Published Version (Please cite this version)
10.1371/journal.pone.0002347Publication Info
Yeo, Tsin W; Lampah, Daniel A; Gitawati, Retno; Tjitra, Emiliana; Kenangalem, Enny;
Granger, Donald L; ... Anstey, Nicholas M (2008). Safety profile of L-arginine infusion in moderately severe falciparum malaria. PLoS One, 3(6). pp. e2347. 10.1371/journal.pone.0002347. Retrieved from https://hdl.handle.net/10161/4494.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joe Brice Weinberg
Professor 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 inflamm

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