Use of a pharmacokinetic/pharmacodynamic model to design an optimal dose input profile.

摘要: A model for the pharmacodynamic effect of a drug (designated only X), and use to explore optimal input is described. The data analyzed here are from crossover comparison study 4 active treatments, yielding distinct concentration vs. time curves, plus placebo in 32 subjects. expresses total as sum (pure) effect. latter allows possible tolerance (found) effects (not found). Random allow interindividual differences be expressed. Conditioning on fitted model, population profile designed that obeys certain protocol constraints. minimizes expectation squared between target resulting response over given interval. fixed constant, chosen either individuals' maximum level baseline regimen used or typical individual this regimen, predicted model. taken estimated nonparametric distribution subjects' random effects. As one goal early clinical studies drugs may provide basis designing an delivery (with respect specified loss function), we suggest report example reasonable way go about finding such profile.