Application of the Loo-Riegelman absorption method

The Loo-Riegelman absorption method provides the correct A/V₁ value and the correct rate constant k_a (if absorption is first order), whether metabolism occurs in compartment 1 only, compartment 2 only, or both compartments 1 and 2 of the two-compartment open model. In cases where there is metabolism in compartment 2, the disposition parameters estimated from intravenous data are only apparent and not the real values. The correct A/V₁ and k_a values are obtained, however, only under conditions not hithertofore specified. These conditions are that there must be essentially no bias in the disposition parameters k₁₂, k₂₁, and k_el. and in the C₀ value estimated from the intravenous data, and that in the oral study a large number of interpolated plasma concentrations, as well as the observed plasma concentrations, must be used, especially for drugs with long half-lives. It is shown that application of the Guggenheim method to the initial A₁ V₁, tvalues frequently provides a better method of estimating A/V₁ and k_a than the classical method. If biased disposition parameters are used in application of the Loo-Riegelman method to oral data, then essentially the correct value of k_a will be estimated, but the estimate of A/V₁ will be approximately equal to the true value of A/V₁ multiplied by the ratio of the biased C₀ value (obtained in fitting the intravenous data) to the true C₀ value of the intravenous data. The above indicates that intravenous data should be fitted by computer until there are no systematic deviations or trends and as small a sum of squared deviations as possible is obtained. The oral data should be fitted by spline or Akima methods, or similar procedures, to produce a function which passes through each observed plasma concentration and at the same time provides a large number of interpolated concentration data.Partly supported by Public Health Service Grant 5-P11-GM15559.