A simulation-based confidence band for drug concentrations in blood: an application to a clinical phase I trial.

Since drug concentrations in blood are usually related to the effectiveness and toxicity, a confidence band for the drug concentrations gives useful information for the treatment. This paper proposes a simulation-based approach for constructing confidence bands for drug concentrations in blood. The confidence band covers the whole profile of the drug concentrations with a specified probability. The proposed approach presupposes that actual concentrations of a subject fluctuate randomly around a curve specified by an appropriate pharmacokinetic model and the subject-specific pharmacokinetic parameters. The confidence band is constructed by taking into account both the random fluctuations of the actual concentrations and the statistical uncertainty of the parameter estimates. The proposed approach is applied to a simulation study and an actual phase I trial.