Use of metzler's NONLIN program for fitting discontinuous absorption profiles

An alternative to the use of integral hybrid flow/compartmental model (HFCM) equations in fitting cases I and II discontinuous absorption profiles is presented. It is proposed that HFCM-integral equations be replaced by a system of differential equations in which sequential sets of equations describe the absorption profile from time zero to infinity. The required sets of differential equations for these two cases are presented as they apply to a two-compartment drug, potentially undergoing multiple absorption steps. It was shown that the use of the NONLIN program in the differential equation mode provides good fits for some unusually shaped absorption profiles of buformin, sulfisoxazole, and griseofulvin. The values of the parameter estimates and the sum of squared deviations, sigma SD, obtained with NONLIN were almost identical to those obtained with the FITS12 program utilizing HFCM equations. While HFCM-integral equations required less computer time, they introduced the potential for negative absorption times. This problem is avoided by use of the differential equations method.