Pharmacogenetics of antimalarial drugs: effect on metabolism and transport.
The prevention and management of malaria is primarily based on the use of drugs. Clinical trials have however revealed that between individuals there is large variability in the pharmacokinetic profiles of many antimalarial drugs. The resulting variations in concentrations of the drug within plasma might lead to either suboptimum effectiveness or drug toxicity in some patients. The evidence is increasing that polymorphically expressed drug-metabolising enzymes, predominantly various cytochrome P450 isozymes but also drug transporters, might contribute to the variability in drug response (incomplete cure, relapse, or resistance) or toxicity experienced with antimalarial drugs. For example, there is a clear association between concentrations of proguanil within plasma and certain genetic polymorphisms of CYP2C19, and genetically established levels of CYP2C8 might have important clinical implications in the toxicity of amodiaquine. Variation in the expression of drug-metabolising enzymes and transport proteins affects the pharmacology of antimalarial drugs. Exploration of pharmacogenetics might help to optimise the use of antimalarial drugs.
Kerb
Reinhold
R
Pharmacogenetics, Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. reinhold.kerb@ikp-stuttgart.de
Fux
Richard
R
Mörike
Klaus
K
Kremsner
Peter G
PG
Gil
José Pedro
JP
Gleiter
Christoph H
CH
Schwab
Matthias
M
D000962:Antimalarials / Q000493:pharmacokinetics*; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D027361:Organic Anion Transporters / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
D000962:Antimalarials; D027361:Organic Anion Transporters; D003577:Cytochrome P-450 Enzyme System