Hassan Alin M, Björkman A, Landberg-Lindgren A, Ashton M
Department of Biopharmaceutics and Pharmacokinetics, Uppsala University, Sweden.
Trans R Soc Trop Med Hyg. 1992 Jul-Aug;86(4):365-7. doi: 10.1016/0035-9203(92)90220-7.
A 48 h in vitro test of the efficacy of artemisinine, dihydroartemisinine, artemether, mefloquine and chloroquine was carried out against 3 chloroquine-resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India. A sigmoid Emax model was fitted to all in vitro inhibition data for each combination of drug and strain. Strains K1 and LS21 were strongly resistant to chloroquine, whereas T996 was partially resistant. Artemisinine, dihydroartemisinine and artemether were active against all strains, with complete growth inhibition at 10(-7) M. Artemether and dihydroartemisinine were both more potent than artemisinine, with 50% effective (EC50) values of 0.57-1.6 nM and 0.36-3.1 nM respectively; the EC50 of artemisinine was 1.5-6.1 nM for the 3 strains. The EC50 values for mefloquine were 46-185 nM. At higher concentrations, strains K1 and LS21 were fully inhibited, while with strain T996 mefloquine did not fully inhibit even at the highest concentration, 1.28 x 10(-6) M. It is concluded that artemisinine and its derivatives were highly effective against the 3 chloroquine-resistant strains, one of which showed borderline resistance to mefloquine.
针对来自泰国的3种耐氯喹恶性疟原虫菌株（K1和T996株）以及来自印度的LS21株，开展了青蒿素、双氢青蒿素、蒿甲醚、甲氟喹和氯喹的48小时体外药效试验。对每种药物与菌株组合的所有体外抑制数据拟合了S形Emax模型。K1和LS21株对氯喹具有强抗性，而T996株具有部分抗性。青蒿素、双氢青蒿素和蒿甲醚对所有菌株均有活性，在10^(-7)M时可完全抑制生长。蒿甲醚和双氢青蒿素均比青蒿素更有效，50%有效（EC50）值分别为0.57 - 1.6 nM和0.36 - 3.1 nM；3种菌株的青蒿素EC50为1.5 - 6.1 nM。甲氟喹的EC50值为46 - 185 nM。在较高浓度下，K1和LS21株被完全抑制，而对于T996株，即使在最高浓度1.28×10^(-6)M时甲氟喹也未完全抑制。结论是青蒿素及其衍生物对这3种耐氯喹菌株高度有效，其中一种对甲氟喹显示出临界抗性。
