Delay in emergence of mefloquine resistance in Plasmodium berghei by use of drug combinations.
Blood induced Plasmodium berghei infection in Swiss mice was exposed during successive passages to melfloquine alone or melfoquine in combination with dapsone or primaquine or erythromycin, and the level of resistance to melfoquine in four sub-lines was compared at ED90 level. Treatment with mefloquine alone resulted in a 201.14 fold increase in resistance after 21 passages. Use of drug combination (melfoquine + dapsone) delayed the acquisition of resistance as shown by a marginal increase of ED90 by 5.76 fold after 34 passages. Similarly, there was a 17.84 fold increase of resistance after 32 passages involving exposure to mefloquine-primaquine and a 112.28 fold increase after exposure to melfoquine-erythromycin combination for 31 passages. The study emphasizes that rational drug combinations should be developed to protect the melfoquine against the emergence of resistance in P. falciparum cases.
Puri
S K
SK
Central Drug Research Institute, Lucknow, U.P., India.
Dutta
G P
GP
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D003622:Dapsone / Q000008:administration & dosage; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004917:Erythromycin / Q000008:administration & dosage; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D015767:Mefloquine; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*; D011319:Primaquine / Q000008:administration & dosage; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*
D000962:Antimalarials; D011804:Quinolines; D004917:Erythromycin; D003622:Dapsone; D011319:Primaquine; D015767:Mefloquine