A method for evaluating the mean residence times of metabolites in the body, systemic circulation, and the peripheral tissue not requiring separate i.v. administration of metabolite
✍ Scribed by Peter Veng-Pedersen; William R. Gillespie
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 272 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0142-2782
No coin nor oath required. For personal study only.
✦ Synopsis
The evaluation of mean residence times of drugs and metabolites provides a simple measure of the tendency for such substances to remain in various parts of the body.'-7
Most attention has been given to the evaluation of the mean residence times of the parent drug'-' although it is often of interest to evaluate the mean residence times of metabolites. This is especially the case when a metabolite is responsible for, or contributes significantly to, the pharmacological and/or toxicological responses. Apparently all methods proposed for obtaining the mean residence time in the body require a known i.v. administration of the compound (i.e., an i.v. bolus or i.v.
In dealing with metabolites this requirement creates special problems. It may be difficult and very time-consuming to isolate, purify or synthesize the metabolite. The separate i.v. administration of the metabolite may also pose special safety problems. 1. To show that the mean residence time of a metabolite in the body, ibm, the mean residence time of a metabolite in the systemic circulation, is,,,, and the mean residence time of a metabolite in the peripheral tissue, i , , , can all be calculated from an i.v. bolus administration of the parent drug without having to separately administer the metabolite intravenously, thereby overcoming the above problems. 2. To derive the following formulae which enables these residence times to be calculated simply from the concentration profiles of the drug (c(t)) and the The purposes of this communication are: