Solution of the multiple dosing problem using linear programming.

Abstract

A system theoretical approach to drug concentration-time data analysis is introduced after the discussion of some relevant concepts as they are used in system theory. The merits of this approach are demonstrated in multiple dosing problem. It is shown that dosage minimization without stringent constraints does not result in the desired therapeutic effect. In a different optimization the discrepancy between the actual and the desired time-histories of the relevant substance's plasma concentration is minimized. It is shown that both of these optimizations can be reduced to linear programming problems which are easily solvable with today's computers. These methods are demonstrated in a case study of dopaminergic substitution in Parkinson's disease where computer simulations show them to yield excellent results. Finally, the limits of this approach are also discussed.