Please use this identifier to cite or link to this item: https://hdl.handle.net/10137/5423
Email LibraryRMU.DOH@nt.gov.au to ask for this document in a different format
Full metadata record
DC FieldValueLanguage
dc.contributor.authorBrussee, Janneke M-
dc.contributor.authorYeo, Tsin W-
dc.contributor.authorLampah, Daniel A-
dc.contributor.authorAnstey, Nicholas M-
dc.contributor.authorDuffull, Stephen B-
dc.date2015-
dc.date.accessioned2018-05-15T23:00:52Z-
dc.date.available2018-05-15T23:00:52Z-
dc.date.issued2016-
dc.identifier.citationAntimicrobial agents and chemotherapy 2016; 60(1): 198-205-
dc.identifier.urihttps://hdl.handle.net/10137/5423-
dc.description.abstractImpaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations of l-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctive l-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g of l-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens for l-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen for l-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions of l-arginine on NO and microvascular reactivity in severe malaria.-
dc.description.provenanceMade available in DSpace on 2018-05-15T23:00:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2016en
dc.language.isoeng-
dc.titlePharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria.-
dc.typeClinical Trial-
dc.typeJournal Article-
dc.typeObservational Study-
dc.typeResearch Support, Non-U.S. Gov't-
dc.identifier.journaltitleAntimicrobial agents and chemotherapy-
dc.identifier.doi10.1128/AAC.01479-15-
dc.identifier.pubmedidhttps://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/26482311-
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshArginine-
dc.subject.meshBlood Vessels-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshExhalation-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshHumans-
dc.subject.meshMalaria, Falciparum-
dc.subject.meshMale-
dc.subject.meshManometry-
dc.subject.meshMiddle Aged-
dc.subject.meshNitric Oxide-
dc.subject.meshNitric Oxide Synthase Type III-
dc.subject.meshPlasmodium falciparum-
dc.subject.meshSeverity of Illness Index-
dc.identifier.affiliationOtago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands..-
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore Insitute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore..-
dc.identifier.affiliationNational Institute of Health Research and Development-Menzies School of Health Research Malaria Research Program, Timika, Indonesia..-
dc.identifier.affiliationGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia Division of Medicine, Royal Darwin Hospital, Darwin, NT, Australia..-
dc.identifier.affiliationOtago Pharmacometrics Group, School of Pharmacy, University of Otago, Dunedin, New Zealand stephen.duffull@otago.ac.nz..-
dc.identifier.pubmedurihttps://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/26482311-
Appears in Collections:(a) NT Health Research Collection

Files in This Item:
There are no files associated with this item.


Items in ePublications are protected by copyright, with all rights reserved, unless otherwise indicated.