Volume of distribution and loading dose
The volume of distribution (Vd) is an apparent, theoretical volume: the fluid the dose would have to be dissolved in to give the plasma concentration actually measured.
Remember
Work out Vd as the dose divided by the plasma concentration measured straight after a single rapid intravenous injection: about 3 L means the drug is essentially confined to the bloodstream, about 42 L means it has spread through all body water, and far above 42 L means it is held in tissues such as fat. For the same target concentration, a larger Vd needs a larger loading dose (a larger first dose).
Memory aid
think 3, 14 and 42 litres: plasma, then extracellular fluid (about a third of the body's water), then all body water
The benchmarks run from plasma to extracellular fluid to all body water.
The volume of distribution (Vd) is a theoretical volume, not a real space in the body. It can be much larger than the whole body, so think of it as an apparent figure that links the dose to the plasma concentration.
Calculate it as the dose divided by C0, the plasma concentration measured straight after an intravenous bolus (a single rapid injection into a vein). A 500 mg bolus that gives 10 mg per litre means Vd = 50 L.
The benchmarks for a 70 kg adult are about 3 L for plasma, about 14 L for extracellular fluid (the fluid outside the cells, plasma included) and about 42 L for total body water (all the water in the body).
A Vd close to 3 L means the drug is essentially confined to the bloodstream, as with heparin, a large molecule. A Vd only a little above that, such as warfarin at around 8 to 10 L, fits a drug held in the circulation by tight protein binding (drug attached to proteins such as albumin). A Vd near 42 L means the drug has spread through both the extracellular fluid and the cells.
A Vd far above total body water means the drug is sequestered (taken up and held) in tissues such as fat or muscle, which leaves a low plasma concentration. Digoxin, at around 500 L, is the classic example.
A larger Vd calls for a larger loading dose (a larger first dose that reaches the target concentration quickly). For an intravenous dose, the loading dose rises in step with Vd, and a large Vd also means the drug lingers in the body after the last dose.
Key facts
- Formula
- Vd is the dose divided by C0, the plasma concentration straight after an intravenous bolus.
- Close to plasma volume
- A Vd close to plasma volume means the drug is essentially confined to the bloodstream, as with heparin.
- Just above plasma volume
- A Vd only slightly above plasma volume, such as warfarin at around 8 to 10 L, goes with a drug held in the circulation by tight protein binding.
- Close to total body water
- A Vd close to total body water means the drug has spread through both the extracellular fluid and the cells.
- Far above total body water
- A Vd far above total body water, such as digoxin at around 500 L, means the drug is sequestered in tissues such as fat or muscle.
- Loading dose
- For an intravenous dose, the loading dose is Vd times the target plasma concentration, so it rises in step with Vd.
Exam traps
- For the same target concentration, a Vd above total body water does not by itself mean the largest loading dose: the dose rises in step with Vd, so a Vd of 100 L needs only about a fifth of the dose needed at 500 L.
- A drug confined to extracellular fluid would have a Vd near 14 L, so a Vd of about 40 L is almost three times larger and suggests the drug has also entered cells.
- A Vd close to total body water (about 42 L) does not mean the drug is mainly distributed within intracellular fluid (the fluid inside the cells), with little in extracellular fluid, because it supports distribution through both.
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