Antimalarial dosing regimens and drug resistance.
The contribution of underdosing to antimalarial treatment failure has been underappreciated. Most recommended dosage regimens are based on studies in non-pregnant adult patients. Young children and pregnant women, who bear the heaviest malaria burden, have the highest treatment failure rates. This has been attributed previously to lower immunity, although blood concentrations of many antimalarial drugs are significantly lower in pregnant women and young children than in non-pregnant adults. Nevertheless, there have been no studies of higher dosages. Sub-therapeutic concentrations will certainly contribute to poorer responses to treatment and will fuel the emergence and spread of antimalarial drug resistance. There is an urgent need for studies to optimise antimalarial dosage regimens in infants, young children and pregnant women, both to improve cure rates and to prolong the useful therapeutic lives of antimalarial drugs.
Barnes
Karen I
KI
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa. karen.barnes@uct.ac.za
Watkins
William M
WM
White
Nicholas J
NJ
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010961:Plasmodium / Q000187:drug effects*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control; D012307:Risk Factors; D017211:Treatment Failure
D000962:Antimalarials