标题:
Target attainment analysis and optimal sampling designs for population pharmacokinetic study on piperacillin/tazobactam in neonates and young infants
讲者:
陈也伟
单位:
复旦大学附属儿科医院
播放:
1799
论文摘要:
Objectives Population pharmacokinetic (popPK) analyses for piperacillin/tazobactam in neonates and infants of less than 2 months of age have been performed previously. The results indicate that a dose of 44.44/5.56 mg/kg piperacillin/tazobactam every 8 or 12 h may not be enough for controlling infection in this population. In order to determine the appropriate dosing regimen and to provide a rationale for the development of dosing guidelines suitable for this population, further popPK studies of piperacillin/tazobactam would need to be conducted. The aim of the present study was to determine the appropriate dosing regimen and optimal sampling schedules in neonates and infants of less than 2 months of age.
Methods Pharmacodynamic profiling of piperacillin using Monte Carlo simulation was performed to explore the target attainment probability of different dosing regimens for infections caused by different isolated pathogens. D-optimal designs for piperacillin and tazobactam were conducted separately and the time that overlapped were chosen as the final sampling scheme for future popPK studies in neonates and young infants of less than 2 months of age.
Results Our findings revealed that compared to the current empirical piperacillin/tazobactam dose regimen (50 mg/kg every 12h by 5 min infusion in our hospital), the clinical outcome could be improved by increasing doses, increasing administration frequency and prolonging intravenous infusion in neonates and infants of less than 2 months of age. The following optimal sampling windows were chosen as the final sampling scheme: 0.1-0.11, 0.26-0.29, 0.97-2.62 and 7.95-11.9 h administered every 12h, 0.1-0.11, 0.22-0.29, 0.91-1.96 and 5.56-7.93 h administered every 8h, 0.1-0.11, 0.25-0.28, 0.84-1.69 and 4.55-5.94 h administered every 6h.
Conclusions The dosing regimen and sampling schedules proposed in this study should be considered in future popPK studies of piperacillin/tazobactam in neonates and infants. To the best of our knowledge, this is the first study that Monte Carlo simulation and optimal design were used for designing popPK studies of piperacillin/tazobactam.