Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 24

In the blood, a proportion of a drug is bound to plasma proteins – mainly albumin (acidic drugs) and α₁‐acid glycoprotein (basic drugs). Only the unbound, or free, fraction distributes because the protein‐bound complex is too large to pass through membranes. It is the unbound portion that is generally responsible for clinical effects – both the target response and the unwanted adverse effects. Changes in protein binding (e.g. resulting from displacement interactions) generally lead to a transient increase in free concentration but are rarely clinically relevant. However, a lower total concentration will be present and the measurement might be misinterpreted if the higher free fraction is not taken into account. This is a common problem with the interpretation of phenytoin concentrations, where free fraction can range from 10% in a normal patient to 40% in a patient with hypoalbuminaemia and renal impairment.