Shortcomings in Pharmacokinetic Analysis by Conceiving the Body to Exhibit Properties of a Single Compartment

Abstract

In the past, pharmacokinetic assessment of drug absorption, metabolism, and excretion usually have been based on the concept of the body behaving as a single compartment. After rapid i.v. injection, provided that blood samples are taken sufficiently soon after injection, at least a bi-exponential curve is obtained. The initial portion of this curve, the so-called rapid distribution phase, has been ignored without proof, and it has been assumed that the single-compartment concept does not introduce large errors into the subsequent calculations. On the basis of first principles, at least one additional peripheral compartment must exist for virtually any compound introduced into the body. Such a model is physiologically compatible with distribution of the drug throughout the body under perfusion and diffusion forces. The two-compartmental open-system model is discussed in respect to the error introduced into the usual absorption rate and elimination rate calculations and on the estimation of the volume of distribution of various drugs. In the past, pharmacokinetic assessment of drug absorption, metabolism, and excretion usually have been based on the concept of the body behaving as a single compartment. After rapid i.v. injection, provided that blood samples are taken sufficiently soon after injection, at least a bi-exponential curve is obtained. The initial portion of this curve, the so-called rapid distribution phase, has been ignored without proof, and it has been assumed that the single-compartment concept does not introduce large errors into the subsequent calculations. On the basis of first principles, at least one additional peripheral compartment must exist for virtually any compound introduced into the body. Such a model is physiologically compatible with distribution of the drug throughout the body under perfusion and diffusion forces. The two-compartmental open-system model is discussed in respect to the error introduced into the usual absorption rate and elimination rate calculations and on the estimation of the volume of distribution of various drugs.