title: Interaction of artemisinin and tetracycline or erythromycin against Plasmodium falciparum in vitro.
abstract: Antimalarial activities of tetracycline (TC) and erythromycin (EM), alone or in combination with artemisinin (Qinghaosu, QHS), were studied using chloroquine (CQ)-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum in vitro. The antimalarial potency of TC (IC50 = 9862 nM for the CQ-sensitive parasite, 32414 nM for the CQ-resistant one) or EM (IC50 = 45787 nM for the CQ-sensitive parasite, 33397 nM for the CQ-resistant one) was much less than that of QHS (IC50 ranging from 25 to 40 nM). The CQ-resistant falciparum parasite displayed a cross-resistance to TC, while both the drug-sensitive and -resistant parasites exhibited similar responses to EM. However, antimalarial potency of EM appeared to be less than that of TC against the drug-sensitive parasite. When TC was combined with QHS, an additive interaction was observed against the CQ-sensitive falciparum parasite, while synergism was found with the CQ-resistant parasite. When EM was tested in combination with QHS, a potentiating interaction occurred with both the CQ-sensitive and resistant falciparum parasite. The above results indicated that the QHS combination with either TC or EM may be a promising antimalarial preparation with low recrudescence compared to artemisinin used alone in clinical practice.
authors.affiliation: Department of Pharmacology, China Academy of Traditional Chinese Medicine, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
authors.forename: K
authors.initials: K
authors.lastname: Van Dyke
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D004917:Erythromycin / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013752:Tetracycline / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011500:Protein Synthesis Inhibitors; D012717:Sesquiterpenes; D004917:Erythromycin; D002738:Chloroquine; C031327:artemisinin; D013752:Tetracycline