Delay in emergence of resistance to pyronaridine phosphate in Plasmodium berghei
Abstract
Plasmodium berghei ANKA is sensitive to pyronaridine, chloroquine, sulfadoxine an dpyrimethamine. The ED50 of these drugs given by single intragastric doses to infected mice were 2.7, 16.7, 9.1 and 4.3 mg/kg, respectively.
When the parasites of P. berghei ANKA were exposed to 3 structurely different drugs in successive syringe passages in mice, ie, 3 lines of the parasites in each mouse passage were given with ig doses of pyronaridine 4 mg/kg, sulfadoxine 5 mg/kg or pyrimethamine 1 mg/kg, low-level resistance develoed to all 3 lines on passage 31-34. When the parasites were passaged under a drug pressure of triple combination (pyronaridine 2 mg/kg, sulfadoxine 1 mg/kg, and pyrimethamine 0.05 mg/kg), the sensitivity of the parasites of passage 34 to either pyronaridine or the triple combination was virtually similar to that of a normal line of P. berghei ANKA, indicating that the development of resistance to pyronaridiine and the triple combination were greatly inhibited. But the emergence of resistance in P. berghei ANKA was not delayed by chloroquine (27 mg/kg) and pyronaridine (4 mg/kg) given alternately to mice.
A high-degree pyronaridine resistance developed rapidly when P. berghei ANKA was passaged under drug pressure of pyronaridine at high doses. However, under lower drug pressure of pyronaridine (4 mg/kg), no high resistance developed in the parasites of passage 31-45.
Keywords:
When the parasites of P. berghei ANKA were exposed to 3 structurely different drugs in successive syringe passages in mice, ie, 3 lines of the parasites in each mouse passage were given with ig doses of pyronaridine 4 mg/kg, sulfadoxine 5 mg/kg or pyrimethamine 1 mg/kg, low-level resistance develoed to all 3 lines on passage 31-34. When the parasites were passaged under a drug pressure of triple combination (pyronaridine 2 mg/kg, sulfadoxine 1 mg/kg, and pyrimethamine 0.05 mg/kg), the sensitivity of the parasites of passage 34 to either pyronaridine or the triple combination was virtually similar to that of a normal line of P. berghei ANKA, indicating that the development of resistance to pyronaridiine and the triple combination were greatly inhibited. But the emergence of resistance in P. berghei ANKA was not delayed by chloroquine (27 mg/kg) and pyronaridine (4 mg/kg) given alternately to mice.
A high-degree pyronaridine resistance developed rapidly when P. berghei ANKA was passaged under drug pressure of pyronaridine at high doses. However, under lower drug pressure of pyronaridine (4 mg/kg), no high resistance developed in the parasites of passage 31-45.