New Compartment- and Model-Independent method for Rapid Calculation of Drug Absorption Rates

Abstract

A simple and rapid method for the absorption rate calculation for drugs exhibiting linear pharmacokinetics is proposed. The method employs the novel instantaneous midpoint-input principle, which assumes that all drug absorbed during a given interval, regardless of the complexity of the absorption kinetics, is absorbed instantaneously at the midpoint of the interval. The drug amount absorbed is calculated by comparing the net plasma level resulting from the absorption during that interval with the plasma drug level obtained after intravenous dosing at the midpoint of the absorption interval. The method does not assume any compartments or models commonly used in pharmacokinetic studies. In examples with markedly different pharmacokinetic properties, the new method yielded accurate results almost identical to those obtained with the standard Wagner-Nelson and Loo-Riegelman methods. The method often is accurate to two to four significant figures in absorption rate calculations. For first-order absorption, the new method appears to be less subject to the influence of timing of the first blood sample. Theoretically, information on only a small portion of the intravenous plasma level-time profile is sufficient for the analysis. Data on plasma levels shortly after intravenous dosing and the terminal biological half-life are not always needed. Thus, the method might be particularly useful for drugs with long or uncertain biological half-lives. Theoretically, the method also can be applied to urine or saliva data. The method assumes the same drug disposition kinetics between the intravenous and absorption studies.