A model independent approach to describe the blood disappearance profile of intravenously administered drugs.

Abstract

A model independent approach is proposed to describe the blood disappearance profile of intravenously administered drugs. This approach requires a new definition of the total volume of distribution as a function of time. The total volume of distribution is regarded as the sum of V₁ and V₂. V₁ represents the initial volume of distribution after the intravenous administration of drugs. V₂ represents the additional distribution volume where the drug is distributed after the initial rapid distribution has ceased. To characterize V₂, two parameters, the maximum value of V₂, (V₂)_max, and the distribution constant, K_d, which is equal to the time when V₂ is equal to one-half its maximum, are adopted. It has been suggested by a simulation study that these two parameters, (V₂)_max, and K_d, are the major determinants of the rapid initial disappearance (i.e. distribution phase) of drugs from the blood stream after intravenous administration. The blood disappearance profile of warfarin was analyzed on the basis of this approach.