Use of radionuclide tracers in pharmacokinetic studies of antimalarial compounds

To conduct pharmacokinetic and metabolic studies, there is a need for the development of sensitive analytical methods. The analytical methods frequently used to analyse antimalarials are High Performance Liquid Chromatography, Gas Chromatography and Thin-Layer Chromatography. However, in vivo studies that need more specific and sensitive methods to measure major metabolites present in the blood or urine require the use of 14C- or 3H-labelled compounds. The parent drug may be so extensively bio-transformed that the amount of intact drug may be well below the sensitivity limits of the chemical assay methods available. It is therefore crucial for new antimalarials that in vitro biotransformations by microsomal enzyme preparations and/or in vivo studies using labelled compounds be run in parallel with chemical assay developments. In the case of primaquine, extensive metabolic information was obtained when radiolabelled compounds were used in studies of the metabolism of this compound in mammals. The distribution of primaquine in rat tissues was determined by the use of 14C-labelled primaquine diphosphate. Other pharmacokinetic parameters were obtained when HPLC methods were used to measure primaquine in blood. 6 refs, 3 figs, 3 tabs