Chemotherapeutic studies with mefloquine and selection of a mefloquine resistant strain of Plasmodium berghei
Kazim, M.; Puri, S.K.; Dutta, G.P.
Indian Journal of Medical Research 70(Suppl): 95-102
1979
ISSN/ISBN: 0019-5340 PMID: 121298 Document Number: 148913
Mefloquine hydrochloride (WR 142 490) showed high blood schizontocidal activity against a normal strain of Plasmodium berghei in mice, as well as against chloroquine-, pyrimethamine- and primaquine-resistant strains; the chloroquine-resistant strain was the most susceptible to mefloquine. A strain of P. berghei highly resistant to mefloquine was developed by maintaining the strain in weanling rats under increasing drug pressure combined with interrupted subcurative drug therapy. After 9 serial passages the strain was resistant to a total dose of 1216 mg/kg mefloquine (maximum tolerated daily dose), administered over 5 days. The strain gradually lost its resistance to mefloquine over a 31-day period when passaged in rats in the absence of the drug. The resistant strain remained sensitive to normal doses of other antimalarial drugs, except primaquine to which it showed a 2-fold resistance.