Expanded Answers for Study Problems in: Rowland & Tozer's Clinical Pharmacokinetics: Concepts and Applications, 3rd edition.

Chapter 19 - Distribution Kinetics

Study Problems on Page 335-336

1. Volume of distribution at steady-state - This parameter means exactly what its name implies, it is the apparent volume into which a xenobiotic is distributed when the agent has reached steady-state. This is the "purest" volume parameter, as it is a parameter which solely reflects distribution. When drug is administered at a constant rate and the rate of input is equal to the rate of output, the xenobiotic has distributed into all tissues in which it will distribute and has reached equilibrium in those tissues. The discussion on this topic on p. 323-325 of your book does a good job comparing this volume with other volumes terms. So ... READ IT!! (-:

2.a) Frankly, it even takes a finite period of time for xenobiotic to distribute in blood. Homogeneous mixing of an agent throughout blood does not occur instantaneously - even though in all of our kinetic determinations we assume that it does. However, the error introduced by this assumption is essentially insiginificant, with few rare exceptions. It is also unlikely that any drug is entirely limited to vascular space. Thus, all drugs will exhibit a distribution phase. Again, however, for many drugs this phase can be ignored. How do we determine when we cannot ignore this distribution phase? The first case is when there is significant elimination of the drug taking place during the period of distribution. The second is when we desire to model drug concentrations during this phase.

c) After 5 half-lives there is still ~3% of the drug remaining in the body. The significance of this fraction of the dose depends on the agent and the purpose for which elimination is being considered. For example, there may still be detectable concentrations after 5 half-lives. After 7 half-lives less than 1% of the dose remains in the body, which may be a more appropriate approximation of total elimination in some cases.

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