Efficient Pharmacokinetic Modeling of Complex Clinical Dosing Regimens: The Universal Elementary Dosing Regimen and Computer Algorithm EDFAST
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Dosing regimens used in clinical practice are often complex, involving several different routes of administration, dose sizes, dosing rates, and dosing intervals and durations. A novel universal elementary dosing regimen (uedr), that allows general pharmacokinetic modeling of these clinical regimens, is presented and developed mathematically. The uedr concept is computationally efficient, mathematically exact, and logically simple, and can replace the disparate standard concepts and equations of elementary infusion, "bolus" injection, multiple injection, oral dosing, zero-order-release dosing, etc. An optimized computer algorithm (EDFAST) based on the uedr approach, that readily permits the creation of a single fast and versatile microcomputer program for the analysis of all complex dosing regimens in any set of linear compartmental models, is presented. This is of particular relevance to three areas of application in clinical pharmacokinetics: compartmental drug concentration or amount versus time course prediction (simulation) with known model parameter values; parameter estimation (curve-fitting) from measured concentration versus time data; and individualized complex dosing regimen calculation (optimization) for target sets of concentration-time points. Application examples that show the versatility of the uedr approach are presented in detail.