Achieving Concentration Goals with Nonparametric Compartmental Models - the "multiple Model" Design of Dosage Regimens

Multiple model (MM) design and stochastic control of dosage regimens permits essentially full use of all the information contained in either a nonparametric EM (NPEM) population pharmacokinetic model or in an MM Bayesian updated parameter set, to achieve and maintain selected therapeutic goals with optimal precision (least predicted weighted squared error). The regimens are visibly more precise than those developed using mean parameter values. Bayesian feedback has now also been incorporated into the MM software. An evaluation of MM dosage design using an NPEM population model versus dosage design based on conventional mean population parameter values is presented, using a population model of Vancomycin. Further feedback control was evaluated, also incorporating realistic simulated uncertainties in the clinical environment such as those in the preparation and administration of doses.