Evaluation of Two Phenanthrenemethanols for Antimalarial Activity in Man: WR 122,455 and WR 171,669.

摘要

Two phenanthrenemethanols, WR 122,455 and WR 171,669, were examined for oral tolerance, toxicity and efficacy against P. falciparum in man. In healthy subjects, gastrointestinal symptoms limited single day dosage of WR 122,455 to 800 mg and WR 171,669 to 1260 mg. No laboratory abnormalities, phototoxicity or gastrointestinal blood loss were noted in the subjects receiving these drugs. In subjects infected with malaria, WR 122,455 cleared parasitemia when given for one day in doses from 440-880 mg, recrudescences occurred in these subjects who were infected with either chloroquine-sensitive or -resistant P. falciparum. However, WR 122,455 at 480 mg/day for 3-6 days cured 9/9 cases of chloroquine-resistant and 4/4 cases of chloroquine-sensitive P. falciparum infections. WR 171,669 at 1 gram/day for 3 days cured 6/6 subjects with chloroquine-resistant and 3/3 cases of chloroquine-sensitive infections. Both agents cleared parasitemia and fever promptly. (Author)