ABSTRACT
Biochemical aspects of action of antifolates and 4-aminoquinolines and their resistance in the malaria parasites are reviewed, with emphasis on pyrimethamine and chloroquine respectively. Resistance to pyrimethamine has been shown to be associated with either an increase in the amount of parasite dihydrofolate reductase or a reduced affinity of the enzyme for drug binding, in line with the presence of a distinctive pathway for folate metabolism. The theories for drug synergism in the folate pathway are discussed with respect to resistance to pyrimethamine and its combination with sulpha drugs. The biochemical basis for chloroquine resistance is still unclear, reflecting incomplete understanding of its mechanism of action. Data implicating the role of haemozoin and other components as a putative chloroquine receptor of the parasites are reviewed, and possible explanations for resistance are discussed.
Subject(s)
Aminoquinolines/pharmacology , Antimalarials/pharmacology , Chloroquine/metabolism , Drug Resistance, Microbial , Drug Synergism , Folic Acid/metabolism , Folic Acid Antagonists/pharmacology , Hemin/metabolism , Plasmodium/drug effects , Pyrimethamine/pharmacology , Sulfanilamides/pharmacologyABSTRACT
An increased efficacy of liposomes-encapsulated praziquantel was observed in the treatment of hamster opisthorchiasis. A single intracardial dose of 1.5 mg/kg of encapsulated praziquantel is as effective as an intracardial dose of 30 mg/kg or an oral dose of 100 mg/kg of free praziquantel. The suppressing activity of both free and liposomes-encapsulated praziquantel significantly decrease as the infection times increase from 1 to 5 weeks, suggesting that the young liver flukes are more susceptible to praziquantel than the adult flukes.
Subject(s)
Animals , Cricetinae , Isoquinolines/therapeutic use , Liposomes/administration & dosage , Mesocricetus , Opisthorchiasis/drug therapy , Praziquantel/therapeutic useABSTRACT
The dose of praziquantel required to achieve a 100% worm reduction in O. viverrini infected hamsters was found to be 300 mg/kg body weight. The drug was administered orally for 1 day by dividing a total dose into 3 equal doses at 4 h interval. The effect of praziquantel treatment on liver collagen was followed by measuring liver collagen content in at various intervals after administration of the drug. A decrease in collagen content in the infected livers occurred within a few weeks following the treatment suggesting a recovery from liver fibrosis.