Chapter 18 Distribution

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Other Distribution Considerations

Weight considerations

The apparent volume of distribution will often be proportional to the total body weight of a patient. In fact many V values found in the literature will be given as so many liter per kilogram total body weight. The assumption made is that the body composition is unchanged on a percentage basis, thus distribution will be identical no matter what the patient weighs. This works within some limits. For example body composition of the very young and the very old may be quite different from 'normal', that is the average subject in whom the parameter values may have been originally determined. The young and the old will be discussed in more detail later. Another group of patients in which body composition may be greatly altered from `normal' is the obese. These patients have a higher proportion of adipose tissue and lower percentage of water. Thus for drugs which are relatively polar, volume of distribution values may be somewhat lower than the total body weight may suggest. For example the apparent volume of distribution of antipyrine is 0.62 l/kg in normal weight subjects but 0.46 l/kg in obese patients (Abernethy et al., 1981). Other drugs such as digoxin and gentamicin are also quite polar and tend to distribute into water rather than adipose tissue.

Protein binding interactions

The role of protein binding in drug interactions can be quite involved (Rowland and Tozer, 1989). Although drugs may well displace each other from common binding sites, the clinical (and pharmacokinetic) importance of these interactions may require considerable investigation. For these effects to be important one drug must be extensively protein bound, while the displacer must have a high affinity for the same binding site. Therapeutically the major criteria is the free drug concentration. One result of a drug interaction is to tend to produce an increase in free drug concentration, however, that will cause an increase in elimination and thus an overall reduction in total drug concentration, potentially maintaining the free concentrations unchanged.

References

Abernethy, D.R., Greenblatt, D.J, Divoll, M. et al. 1981 Alterations in drug distribution and clearance due to obesity, J.P.E.T., 217, p681-85
Rowland, M and Tozer, T.N. 1989 Clinical Pharmacokinetics, Lea & Febiger, Philadelphia, pp 260-270

Student Objectives for this Chapter

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