AAC
- Dzinjalamala, et al, "Association between the Pharmacokinetics and In Vivo Therapeutic Efficacy of Sulfadoxine-Pyrimethamine in Malawian Children"
- Bhavnani, ..., and Ambrose, PG, "Use of Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To Support Phase 2 and 3 Dosing Strategies for Doripenem"
The integration of phase 1 pharmacokinetic data with nonclinical data from infection models, and the use of the Monte Carlo simulation, allowed us to construct doripenem dosing strategies for further clinical evaluation in phase 2 and 3 (...). When sufficient phase 2 pharmacokinetic data are available, it will be important to use these data to refine the current population pharmacokinetic model and subsequently make more accurate inferences about PK-PD target attainment in patient populations of interest.
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- そして，
Although uncertainty in the estimation of typical values of pharmacokinetic parameter estimates or interindividual variability had little impact on PK-PD target attainment results, two notable and related limitations of these analyses were evident.
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- つまり，phase 1 のデータを用いているので，例数が少ない，対象集団が均質すぎる，特に，腎機能のばらつきが小さい，ということ．
- 何を検討したかというと，
Sensitivity analyses, carried out to assess the magnitude of deviations in PK-PD target attainment for simulations based on the upper and lower confidence bounds versus those based on the central estimates for the pharmacokinetic parameters, failed to show a substantial impact of uncertainty in the estimation of pharmacokinetic parameter typical values or interindividual variabilities.
