Model-independent method of analyzing input in linear pharmacokinetic systems having polyexponential impulse response I: Theoretical analysis.

A rigorous treatment of linear compartmental systems is presented, which allows the input rate of drugs into the systemic circulation to be evaluated without assuming a specific kinetic model. The method allows the input to be evaluated in the presence or absence of any combination of intravenous bolus input and infusion input. Only data for the blood drug concentration are required; there are no requirements for specific sampling times. Applications of the equations are given in several examples. The input rate is evaluated with data obtained from a disposition experiment involving an intravenous bolus or zero-order infusion input and an experiment involving the input to be evaluated. The two experiments can be merged so that the input can be evaluated without a washout period between the two drug administrations. The equations also enable model-independent calculations of the optimal drug input control that produces any desirable drug concentration profile. The approach is a useful deconvolution method for any linear pharmacokinetic system where the impulse response can be approximated by a polyexponential expression.