Document Detail


Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria.
MedLine Citation:
PMID:  11052924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retinol (vitamin A alcohol) is an accepted adjunctive treatment in infections such as measles. There is also indirect evidence from in vitro, animal and human studies that retinol supplementation may be beneficial in severe malaria. There have, however, been no studies that have examined the pharmacokinetics of acute retinol supplementation in severe illness. To establish whether mobilization of intramuscular retinyl palmitate (RP) and its availability as retinol are adequate in complicated falciparum malaria, we administered a single dose of 400000 i.u. of RP to six Vietnamese adults with severe malaria. Another 28 patients were not given RP. All patients had blood samples taken over 96 h for RP and retinol assay using HPLC, and received conventional anti-malarial and supportive therapy. Admission serum retinol concentrations were below the lower limit of the reference range (<1.0 micromol/l) in 74% of the 34 patients. In supplemented patients, analysis of serum RP between 0 and 96 h using a multi-compartmental model revealed a median (range) delay in mobilization of 6.9 h (0.7-15.1 h), a bioavailability of 55% (19-100%) and an elimination half-life of 13.5 h (4.2-23.7 h). The area under the serum retinol curve expressed as an absolute or percentage change from baseline was greater in supplemented than in unsupplemented patients (P<0.05). The separation in median serum retinol concentrations in the two groups was maximal at 48 h. The model-derived retinol half-life [1.5 (0.7-15.8) h] suggested rapid uptake, metabolism and/or excretion. In conclusion, there is variable RP bioavailability in severe malaria, but a significant if delayed increase in serum retinol over that associated with recovery from the infection. In severe infections, RP supplementation appears simple, well tolerated and of potential benefit once anti-microbial and supportive therapy have been established.
Authors:
T M Davis; T Q Binh; L T Thu; R Rossi; P T Danh; P H Barrett; J Beilby
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  99     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2001-01-26     Completed Date:  2001-03-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  433-41     Citation Subset:  IM    
Affiliation:
University of Western Australia, Department of Medicine, Fremantle Hospital, P.O. Box 480, Fremantle, Western Australia 6959, Australia. tdavis@cyllene.uwa.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adult
Antimalarials / therapeutic use
Area Under Curve
Biological Availability
Chromatography, High Pressure Liquid
Drug Therapy, Combination
Half-Life
Humans
Malaria, Falciparum / blood,  drug therapy*
Palmitates / blood,  pharmacokinetics*,  therapeutic use
Vitamin A / blood,  pharmacokinetics*,  therapeutic use
Grant Support
ID/Acronym/Agency:
TW 02272/TW/FIC NIH HHS
Chemical
Reg. No./Substance:
0/Antimalarials; 0/Palmitates; 11103-57-4/Vitamin A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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