Distribution is uneven
Distribution is the spread of drug from blood into the tissues, and it is never uniform. Highly fat-loving drugs pile up in fatty tissue; others bind to proteins floating in the plasma — chiefly albumin. Bound drug is parked: it cannot leave the bloodstream, cannot reach a receptor, and cannot be eliminated. Only the free drug fraction — the unbound portion — is pharmacologically active. Some barriers actively exclude drugs: the blood–brain barrier keeps most molecules out of the brain, which is why a drug that works on the body may do nothing in the central nervous system.
To summarise all this spreading in one number, pharmacologists use the volume of distribution (Vd). It is not a real anatomical volume — it is an *apparent* one. Vd answers: 'If all the drug in the body sat at the concentration we measure in plasma, how big a tank of fluid would hold it?' A small Vd means the drug stays mostly in the blood; a huge Vd means most of it has fled into tissues, leaving little in the plasma to measure.
Volume of distribution (Vd)
total amount of drug in body
Vd = -------------------------------------
concentration in plasma
Example
Dose in body: 500 mg
Plasma conc: 10 mg/L
Vd = 500 / 10 = 50 L (more than blood volume,
so much sits in tissues)
Small Vd (~5 L) -> stays in blood
Large Vd (>40 L) -> hides in tissue/fatMetabolism: the liver's two-phase workshop
Biotransformation (drug metabolism) usually makes a drug more water-soluble so the kidneys can flush it out. The liver does most of this work in two stages. Phase I reactions — oxidation, reduction, hydrolysis — tweak the molecule, often adding or exposing a reactive chemical handle. The workhorses here are the cytochrome P450 enzymes, a family that handles the majority of drugs. Phase II reactions then bolt a large water-loving group (like glucuronic acid) onto that handle, producing a bulky, very water-soluble product ready for excretion.