title: Plasmodium falciparum: induction of resistance to mefloquine in cloned strains by continuous drug exposure in vitro.
abstract: A genetically homogeneous population of Plasmodium falciparum prepared by a single erythrocyte micromanipulation technique was used to produce lines of P. falciparum resistant to mefloquine hydrochloride in vitro. Parasites were maintained in a culture medium containing gradually increased concentrations of mefloquine hydrochloride (CMP-mef) starting with 2 ng/ml. One of the mefloquine-resistant culture lines (W2-mef) was obtained after 96 weeks of continuous culture in CMP-mef, the last 4 weeks in medium containing 40 ng/ml of mefloquine hydrochloride. The W2-mef was four to six times more resistant to mefloquine than was the parent clone W2. Means of multiple determinations of 50% inhibitory concentrations (IC-50) of mefloquine hydrochloride against W2-mef and clone W2 were 20.39 +/- 5.08 ng/ml and 4.50 +/- 1.94 ng/ml, respectively.
authors.affiliation: Department of Parasitology and Laboratory Practice, School of Public Health, University of North Carolina, Chapel Hill 27514.
authors.forename: A M
authors.initials: AM
authors.lastname: Oduola
authors.forename: W K
authors.initials: WK
authors.lastname: Milhous
authors.forename: N F
authors.initials: NF
authors.lastname: Weatherly
authors.forename: J H
authors.initials: JH
authors.lastname: Bowdre
authors.forename: R E
authors.initials: RE
authors.lastname: Desjardins
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003470:Culture Media; D004351:Drug Resistance; D007527:Isoenzymes / Q000032:analysis; D015767:Mefloquine; D010616:Phenanthrenes / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D003470:Culture Media; D007527:Isoenzymes; D010616:Phenanthrenes; D011725:Pyridines; D011804:Quinolines; D002084:Butylated Hydroxytoluene; C012496:alpha-(2-piperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrenemethanol; C039723:WR 184806; C017813:WR 172435; C044656:WR 194965; C023767:enpiroline; C023768:halofantrine; D015767:Mefloquine