Jungbluth G L, Wirth F H, Rubio T T, Janicke D M, Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo.
Dev Pharmacol Ther. 1988;11(6):317-21. doi: 10.1159/000457710.
The disposition of mezlocillin was evaluated in 4 newborn infants in a sequential two-phase study at postnatal ages of 1 day and 8 or 10 days. Renal function was estimated by creatinine clearance (CLCR) and pharmacokinetic parameters of mezlocillin was were determined from serum concentrations and urinary excretion rates. All weight-normalized mezlocillin clearances (total, renal, and nonrenal) and CLCR were less than adult values, but increased after 8 or 10 days of mezlocillin therapy and postnatal development. The volume of distribution at steady state did not significantly change throughout this period, and approximated the expanded extracellular fluid volume typically found in neonates. The elimination half-lives were substantially shorter by phase II of the study. Both renal and nonrenal elimination processes were enhanced by 1 week of postnatal development even though body weight did not increase. Mezlocillin disposition in neonates is thus affected by body weight, gestational age, and postnatal age.
在一项针对4名新生儿的序贯两阶段研究中，在出生后1天以及8或10天时评估了美洛西林的处置情况。通过肌酐清除率（CLCR）评估肾功能，并根据血清浓度和尿排泄率确定美洛西林的药代动力学参数。所有体重标准化的美洛西林清除率（总清除率、肾清除率和非肾清除率）以及CLCR均低于成人值，但在美洛西林治疗8或10天以及出生后发育后有所增加。在此期间，稳态分布容积没有显著变化，并且接近新生儿中通常发现的扩大的细胞外液容积。到研究的第二阶段，消除半衰期显著缩短。即使体重没有增加，出生后1周肾和非肾消除过程均增强。因此，新生儿中美洛西林的处置受体重、胎龄和出生后年龄的影响。
