Active Ingredient: Ivermectin
By consequence, failure to adjust to weight but also for decreased hepatic clearance could theoretically lead to higher than expected ivermectin exposure and toxicity in neonates and infants.
Ivermectin's metabolites are present at very low concentration, which makes isolation and structural characterization challenging.
The correlation of both systems is good in several species tested. Plasma metabolites are less polar than the parent drug and could be fatty acid ester conjugates of the monosaccharides or aglycone of the parent drug.
There is, however, a theoretical possibility of interaction with CYP 3 A 4 inhibitors such as protease inhibitors or inducers such as rifampicin.
Ivermectin is both a substrate and a potent inducer of the P-gp. P-gp plays a role in the transportation of ivermectin to the intestinal lumen and in preventing its crossing of the blood-brain barrier.
P-gp inhibitors such as antifungal azoles can increase ivermectin plasma levels in animals.
The drug—drug interactions of ivermectin with artemisinin-based combination therapy ACT have not been well explored.
The evidence supporting this lethal effect has been reviewed extensively and will not be re-visited here see Additional file 1 for all studies.
However, studies to assess the efficacy of ivermectin in reducing the survival of mosquitoes are not standardized. A typical approach is to allow a sample of vectors to feed on blood containing the drug or on a treated subject.
Resulting mortality is assessed at intervals and reported in different formats. The LC 50 will vary according to the time point chosen for the mortality assessment.
At a given drug concentration and mosquito species, the 3-day LC 50 will be higher than the 9-day LC 50. An alternative approach would be to determine the time to median mortality at any given concentration, but this has not been commonly used.
The feeding method used to determine the LC 50 could also influence the measurement outcome. Ivermectin is highly lipophilic, it is found in higher concentrations in dermal and adipose tissue than venous plasma.
Pharmacokinetic considerations regarding efficacy The efficacy of ivermectin to reduce transmission is expected to be a function mainly of its lethality to the vector population.
Additionally, older mosquitoes seem to be more susceptible to ivermectin that their younger counterparts. Both lethality and sublethal effects will be closely related to drug concentration in reached in the blood of treated individuals and to the time this blood concentration is sustained.
All the concepts defined here refer to the mortality of mosquitoes feeding on a single treated person.
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