02.02.4 Volume of Distribution
The volume of distribution of a drug or the (apparent) volume of distribution, as it is sometimes called, is not a real distribution, but a parameter that is useful in determining whether haemodialysis can be used to rid the body of a particular drug or whether a loading dose of a drug is necessary (loading doses are discussed in chapter 6.4). The (apparent) volume of distribution Vd is defined as the volume of fluid required to contain the total amount of drug in the body, at the same concentration as in the plasma. The volume of distribution will be calculated for us when the drug is first developed. Thus, we don’t need to know how to calculate it, but we do need to know how to interpret it. For instance, compare Drugs A and B, each administered at 100 mg. They may have different distributions and therefore different volumes of distribution. If after administration Drug A has a plasma level of 20 mg/ml, and Drug B has a plasma level of 2 mg/ml – it is obvious that Drug B is more widely distributed than Drug A. That is, more of Drug B is distributed outside of the plasma. For Drug A, Vd is 100 mg/20 mg = 5 L, and for Drug B, Vd is 100 mg/2 mg = 50 L.
The plasma volume in a 70 kg adult = 3L (i.e. ~0.04 L/kg). Any drug that is confined to plasma will have similar volume of distribution to the plasma (0.04 L/kg). Drugs that are evenly distributed throughout body (go everywhere at same concentration as plasma) have a Vd of 0.57 L/kg. Drugs that are accumulated in tissues have a greater volume of distribution.
A low volume of distribution indicates that a drug is largely confined to plasma, and can be removed by haemodialysis. Conversely, drugs with a large Vd will be accumulated in fat or elsewhere, and cannot be removed by haemodialysis, which only removes drugs from blood. For instance, heparin is mainly confined to blood, has a Vd of 0.06 L/kg, and can be removed by haemodialysis. Conversely, the antidepressant nortriptyline has a Vd of 14 L/kg, due to tissue binding outside of the blood stream, and cannot be removed by haemodialysis. Unfortunately, most lipid soluble drugs e.g. amiodarone have high volumes of distribution, due to accumulation in fat tissues, and cannot be removed by haemodialysis.