早产儿替卡西林-克拉维酸的药代动力学。
Pharmacokinetics of ticarcillin-clavulanate in premature infants.
机构信息
Duke University Medical Center, Durham, NC, USA.
Duke Clinical Research Institute, Durham, NC, USA.
出版信息
Br J Clin Pharmacol. 2019 May;85(5):1021-1027. doi: 10.1111/bcp.13882. Epub 2019 Mar 6.
Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6-44 days) and gestational age of 25 weeks (23-28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA ≥14-45 days (0.078 L/kg/h [0.047-0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA ≥ 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration ≤16 μ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 μg/mL), increased dosing frequency or extended infusion are necessary.
替卡西林-克拉维酸涵盖了早产儿中常见的广泛病原体。在胎龄<30 周的婴儿中，缺乏指导替卡西林-克拉维酸剂量的药代动力学数据。我们招募了 15 名胎龄<30 周的早产儿，确定了药代动力学参数，并进行了剂量模拟，以确定替卡西林-克拉维酸的最佳剂量。婴儿的平均（范围）出生后年龄（PNA）为 18 天（6-44 天），胎龄为 25 周（23-28 周）。与 PNA≥14-45 天（0.078 L/kg/h [0.047-0.100]）相比，PNA<14 天的婴儿清除率较低（0.050 L/kg/h [0.043-0.075]），这与肾功能的成熟一致。剂量模拟确定，替卡西林 75mg/kg q12h（PNA<14 天）或 q8h（PNA≥14-45 天）在>90%的模拟婴儿中可实现对最低抑菌浓度≤16μg/mL 的病原体的目标暴露。对于高度耐药的病原体（最低抑菌浓度 32μg/mL），需要增加给药频率或延长输注时间。
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