[Clinical Pharmacological Research Aiming to Optimize Therapeutic Strategies in Specific Populations].

Abstract

In the field of drug development, pharmacokinetic studies primarily focus on adult and pediatric populations, resulting in limited pharmacokinetic data for specific populations such as neonates, pregnant women, and critically ill patients. Optimizing drug therapy for these populations requires dosing strategies that are personalized for individual patients, and are based on pharmacokinetic/pharmacodynamic analyses and therapeutic drug monitoring. In our study of patients admitted to intensive care unit (ICU), the pharmacokinetic parameters of doripenem differed from those in non-ICU patients, with higher pharmacokinetic/pharmacodynamic breakpoints in ICU patients. Population pharmacokinetic modeling of doripenem revealed that prolonged infusion for 4 h was necessary for critically ill patients undergoing continuous renal replacement therapy. In patients with hematological malignancies, inflammatory markers such as C-reactive protein (CRP) significantly affected the intra-individual pharmacokinetic variability of voriconazole, highlighting the need for dose titration according to CRP levels. Furthermore, febrile neutropenia (FN) significantly increased vancomycin clearance in children, requiring higher daily doses than in children without FN. In contrast, augmented renal clearance, but not FN, significantly affected teicoplanin clearance in adults. Physiologically based pharmacokinetic modeling of sublingual buprenorphine facilitated prediction of drug exposure in pregnant women and their fetuses. Post hoc optimization of sublingual absorption using concentrations observed in the mothers markedly improved prediction of fetal exposure. These findings underscore the importance of personalized pharmacokinetic assessments to improve individualized therapeutic strategies in specific populations, and to aim for optimizing efficacy while minimizing adverse effects. Future research integrating mathematical modeling and simulation techniques is expected to improve dosing precision.