Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria

Retinol (vitamin A alcohol) is an accepted adjunctive treatment in infectio ns such as measles. There is also indirect evidence from in vitro, animal a nd human studies that retinol supplementation may be beneficial in severe m alaria. There have, however, been no studies that have examined the pharmac okinetics of acute retinol supplementation in severe illness. To establish whether mobilization of intramuscular retinyl palmitate (RP) and its availa bility as retinol are adequate in complicated falciparum malaria, we admini stered a single dose of 400 000 i.u. of RP to six Vietnamese adults with se vere 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 <mu >mol/l) in 74% of the 34 patients. In supplemented patients, analysis of se rum RP between 0 and 96 h using a multi-compartmental model revealed a medi an (range) delay in mobilization of 6.9 h (0.7-15.1 h), a bioavailability o f 55% (19-100%) and an elimination half-life of 13.5 h (4.2-23.7 h). The ar ea under the serum retinol curve expressed as an absolute or percentage cha nge from baseline was greater in supplemented than in unsupplemented patien ts (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 conclu sion, there is variable RP bioavailability in severe malaria, but a signifi cant if delayed increase in serum retinol over that associated with recover y from the infection. In severe infections, RP supplementation appears simp le, well tolerated and of potential benefit once anti-microbial and support ive therapy have been established.