About extraction ratioWatch
2) Variation of plasma protein binding:
a) for drugs with low extraction ratio: only unbound drug penetrates membranes and is available for elimination. An increase of the unbound fraction will thus proportionally increase the clearance. Therefore, the unbound drug concentration remains constant and no adaptation of the dosage regimen is required.
b) for drugs with high extraction ratio: the organ is capable of removing all the drug presented to it, independently of plasma binding. Therefore, even if the fraction of unbound drug increases, the clearance remains constant and the unbound concentration then increases and may lead to toxicity.
3) Variation of the organ's intrinsic ability to eliminate the drug:
For a low extraction drug, why organ clearance is poorly influenced by blood flow and protein binding? Does not the extraction rate is determined by blood flow ? (organ clearance = blood x extraction ratio)