Trial reportAntimicrobial agents and chemotherapy2008
Pharmacokinetics of L-arginine in adults with moderately severe malaria.
Trial report in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Evaluation of the Interaction of Amino Acid Infusion onClinical pharmacokinetics · 2019Trial
- A randomized pilot study of L-arginine infusion in severe falciparum malaria: preliminary safety, efficacy and pharmacokinetics.PloS one · 2013Trial
- Association betweenAntioxidants (Basel, Switzerland) · 2023Review
- Population Pharmacokinetic Model of AST-001, L-Isomer of Serine, Combining Endogenous Production and Exogenous Administration in Healthy Subjects.Frontiers in pharmacology · 2022Article
- Therapeutic Potential of Citrulline as an Arginine Supplement: A Clinical Pharmacology Review.Paediatric drugs · 2020Review
- Sphingosine 1-Phosphate in Malaria Pathogenesis and Its Implication in Therapeutic Opportunities.Frontiers in cellular and infection microbiology · 2020Review
- Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe PediatricInfection and immunity · 2019Observational
- Reversal of cerebrovascular constriction in experimental cerebral malaria by L-arginine.Scientific reports · 2018Article
- Tetrahydrobiopterin Supplementation Improves Phenylalanine Metabolism in a Murine Model of Severe Malaria.ACS infectious diseases · 2016Article
- Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria.Antimicrobial agents and chemotherapy · 2016Observational
- The evidence for a role of vasospasm in the pathogenesis of cerebral malaria.Malaria journal · 2015Review
- Vascular dysfunction as a target for adjuvant therapy in cerebral malaria.Memorias do Instituto Oswaldo Cruz · 2014Review
- Malaria-associated L-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal Salmonella bacteremia.Infection and immunity · 2013Article
- Cytoadherence and severe malaria.The Malaysian journal of medical sciences : MJMS · 2012Article
- Efficacy of different nitric oxide-based strategies in preventing experimental cerebral malaria by Plasmodium berghei ANKA.PloS one · 2012Article
- Arginases and arginine deficiency syndromes.Current opinion in clinical nutrition and metabolic care · 2012Review
- Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria.The Journal of infectious diseases · 2009Article
- Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications.Expert reviews in molecular medicine · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Severe malaria is associated with decreased nitric oxide (NO) production and low plasma concentrations of L-arginine, the substrate for NO synthase. Supplementation with L-arginine has the potential to improve NO bioavailability and outcomes. We developed a pharmacokinetic model for L-arginine in moderately severe malaria to explore the concentration-time profile and identify important covariates. In doses of 3, 6, or 12 g,L-arginine was infused over 30 min to 30 adults with moderately severe malaria, and plasma concentrations were measured at 8 to 11 time points. Patients who had not received L-arginine were also assessed and included in the model. The data were analyzed using a population approach with NONMEM software. A two-compartment linear model with first-order elimination best described the data, with a clearance of 44 liters/h (coefficient of variation [CV] = 52%) and a volume of distribution of 24 liters (CV = 19%). The natural time course of L-arginine recovery was described empirically by a second-order polynomial with a time to half recovery of 26 h. The half-life of exogenous L-arginine was reduced in patients with malaria compared with that for healthy adults. Weight and ethnicity were significant covariates for clearance. MATLAB simulations of dosing schedules for use in future studies predicted that 12 g given over 6, 8, or 12 h will provide concentrations above the K(m) of endothelial cell CAT-1 transporters in 90%, 75%, and 60% of patients, respectively.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.