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 µmol/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.
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Research Article|
October 19 2000
Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria
Timothy M. E. DAVIS;
*University of Western Australia, Department of Medicine, Fremantle Hospital, P.O. Box 480, Fremantle, Western Australia 6959, Australia
Correspondence: Professor T. M. E. Davis (e-mail [email protected]).
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Tran Quang BINH;
Tran Quang BINH
†Tropical Diseases Research Centre, Cho Ray Hospital, Ho Chi Minh City, Vietnam
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Le The Anh THU;
Le The Anh THU
†Tropical Diseases Research Centre, Cho Ray Hospital, Ho Chi Minh City, Vietnam
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Ric ROSSI;
Ric ROSSI
‡The Western Australian Centre for Pathology and Medical Research, QEII Medical Centre, Hospital Avenue, Nedlands, Western Australia 6009, Australia
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Phan Thi DANH;
Phan Thi DANH
†Tropical Diseases Research Centre, Cho Ray Hospital, Ho Chi Minh City, Vietnam
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P. Hugh R. BARRETT;
P. Hugh R. BARRETT
*University of Western Australia, Department of Medicine, Fremantle Hospital, P.O. Box 480, Fremantle, Western Australia 6959, Australia
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John BEILBY
John BEILBY
‡The Western Australian Centre for Pathology and Medical Research, QEII Medical Centre, Hospital Avenue, Nedlands, Western Australia 6009, Australia
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Publisher: Portland Press Ltd
Received:
January 28 2000
Revision Received:
May 19 2000
Accepted:
June 22 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (5): 433–441.
Article history
Received:
January 28 2000
Revision Received:
May 19 2000
Accepted:
June 22 2000
Citation
Timothy M. E. DAVIS, Tran Quang BINH, Le The Anh THU, Ric ROSSI, Phan Thi DANH, P. Hugh R. BARRETT, John BEILBY; Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria. Clin Sci (Lond) 1 November 2000; 99 (5): 433–441. doi: https://doi.org/10.1042/cs0990433
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