New method that gives true least squares fit of one and two compartment open pharmacokinetic models applied to valproic acid and methadone.

Methods for obtaining an exact least squares fit of the one and two compartment models have not been previously described. The multi compartment polyexponential pharmacokinetic models have classically been fit to data using nonlinear regression programs such as NonLin (Metzler, 1969). The two compartment open model, for example, can be fit to least squares regression with equation 1 by iteratively varying A, alpha, B, and beta. Y = Ae(-alpha t) + Be(-beta t).