Watkins W M, Sixsmith D G, Chulay J D
Ann Trop Med Parasitol. 1984 Jun;78(3):273-8. doi: 10.1080/00034983.1984.11811816.
Using an in vitro radioisotopic method, the activity was measured of proguanil, its metabolites cycloguanil and p-chlorophenylbiguanide (PBG), pyrimethamine, and chloroquine against seven Kenyan and three South East Asian strains of Plasmodium falciparum. Five Kenyan isolates were sensitive to both pyrimethamine and cycloguanil in vitro, while the Smith and two Kenyan strains were resistant to both these drugs. Cross-resistance was incomplete: the Camp strain was resistant to pyrimethamine but not cycloguanil, and the FVO strain was resistant to cycloguanil but not pyrimethamine. Both proguanil and PBG exhibited weak antimalarial activity in vitro, but inhibitory blood levels of either compound are unlikely to occur after a normal human dose of proguanil. The results indicate that the activity of proguanil against P. falciparum is due entirely to the action of its active metabolite cycloguanil.
采用体外放射性同位素方法，测定了氯胍、其代谢产物环氯胍和对氯苯双胍（PBG）、乙胺嘧啶及氯喹对7株肯尼亚恶性疟原虫和3株东南亚恶性疟原虫的活性。5株肯尼亚分离株在体外对乙胺嘧啶和环氯胍均敏感，而史密斯株和2株肯尼亚株对这两种药物均耐药。交叉耐药不完全：坎普株对乙胺嘧啶耐药但对环氯胍不耐药，FVO株对环氯胍耐药但对乙胺嘧啶不耐药。氯胍和PBG在体外均表现出较弱的抗疟活性，但正常人体服用氯胍剂量后，这两种化合物的抑制性血药浓度不太可能出现。结果表明，氯胍对恶性疟原虫的活性完全归因于其活性代谢产物环氯胍的作用。
