ABSTRACT
The present study, carried out in 1987 in Thailand, has been designed to validate the in vitro microtest system, standardized by the World Health Organization (WHO), for the new antimalarials pyronaridine and halofantrine. The sensitivity of naturally acquired, multiresistant populations of Plasmodium falciparum has been assessed in order to develop a data base for further longitudinal investigations. For both drugs the in vitro microtest system seems to be suitable. The concentration range of plates can be considered as almost ideal for pyronaridine (0.1-6.40 mumol/l) while for halofantrine (0.002-0.128 mumol/l) an upward extension of the concentration range would be appropriate. Validation studies with artemisinin demonstrated the need for revising the protocol for the production of the dosing solutions. In the light of current knowledge about therapeutic concentration levels it would probably be appropriate to adopt a range of 0.2-12.8 mumol/l. All tested isolates, except possibly three, showed sensitive responses to pyronaridine. The high EC99 value of halofantrine could be indicative of some resistance to this drug. Rank correlation analysis suggested cross-resistance of pyronaridine and chloroquine which could be of consequence for the future introduction of pyronaridine.