QUESTION
Why do some antimalarial drugs have long therapeutic life while others have short therapeutic lives?
ANSWER
Different anti-malarial drugs target slightly different aspects of the malaria Plasmodium parasite, and so are made with different chemical structures.
The differences in therapeutic life across different malaria drugs has to do with the specific pharmacokinetic properties of the chemical compounds from which the drugs are made. Even drugs designed around the same principal chemical compound can persist for different amounts of time in the human body, depending on the other chemicals with which the active compound is bound. The length of time it takes for a chemical compound to halve in concentration, or for its pharmacological effect to reduce by half, in the human blood stream is known as its “half life.”
For example, the common anti-malarial drug chloroquine has a half life of about 10 days, and is based on a chemical compound called 4-aminoquinoline. However, another drug also based on 4-aminoquinoline, called amodioquine, has a half life of only 10 hours.
Proguanil (combined with atovaquone in the drug Malarone) is dihydrofolate reductase inhibitor with a half life of about 16 hours, while mefloquine (sold as Lariam), is made from quinoline methanol and has a half life ranging from 10-40 days. These differences in length of therapeutic action also affect the efficacy of the compounds against malaria at various stages in its progression, and can also be implicated in the propensity to resistance developing to the drug in the malaria parasite.
It is evident that drugs with a pleiotropic (multiple) mode of action like mefloquine confer a longer useful therapeutic life (UTL) whereas drugs with single putative targets have a shorter UTL.