• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Archives of disease in childhood. Fetal and neonatal edition >Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube
【24h】

Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube

机译：通过鼻胃管给药后患有肺动脉高压的新生儿西地那非暴露

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Objective: To describe the pharmacokinetics and exposure of oral sildenafil (SIL) in neonates (2-5 kg) with pulmonary hypertension (PH). Design: We included 11 neonates (body weight 2-5 kg, postnatal age 2-121 days) who received SIL and extracorporeal membrane oxygenation (ECMO) treatment for PH. SIL capsules were given via a nasogastric tube. Blood samples were collected via a pre-existing arterial line to quantify SIL and metabolite plasma levels (219 samples). Non-linear mixed effects modelling was used to describe SIL and desmethylsildenafil (DMS) pharmacokinetics. Results: A one-compartment model was suitable for SIL and DMS. Interpatient and intrapatient variability for clearance at 100% bioavailability were 87% and 27% (SIL) and 62% and 26% (DMS). Patient weight, postnatal age and post-ECMO time did not explain variability. Concomitant fluconazole use was associated with a 47% reduction in SIL clearance. The exposure expressed as average plasma concentration area under the curve over 24 h (AUC24 (SIL+DMS)) ranged from 625 to 13 579 ng/h/ml. An oral dose of 4.2 mg/kg/24 h would lead to a median AUC 24 (SIL+DMS) of 2650 ng/h/ml equivalent to 20 mg three times a day in adults. Interpatient variability was large, with a simulated AUC 24 (SIL+DMS) range (10th and 90th percentiles) of 1000-8000 ng/h/ml. Conclusions: SIL pharmacokinetics are highly variable in post-ECMO neonates and infants. In a median patient, the current dose regimen of 0.5-2.0 mg/kg four times a day leads to an exposure comparable to the recommended adult dose of 20 mg four times a day. Careful dose titration, based on efficacy and the occurrence of hypotension, remains necessary. Follow-up research should include appropriate pharmacodynamic endpoints, with a population pharmacokinetic/ pharmacodynamic analysis to assign a suitable exposure window or target concentration.
机译：目的：描述口服西地那非（SIL）在肺动脉高压（PH）的新生儿（2-5 kg）中的药代动力学和暴露情况。设计：我们包括11名新生儿（体重2-5公斤，出生后2至121天）接受SIL和PH的体外膜氧合（ECMO）治疗。通过鼻胃管给予SIL胶囊。通过预先存在的动脉管线采集血液样本以定量SIL和代谢产物血浆水平（219个样本）。非线性混合效应模型用于描述SIL和去甲基西地那非（DMS）的药代动力学。结果：单室模型适用于SIL和DMS。在100％生物利用度下，患者间和患者内清除率的变异性分别为87％和27％（SIL），62％和26％（DMS）。患者体重，出生年龄和ECMO后时间不能解释变异性。氟康唑的同时使用可使SIL清除率降低47％。 24小时内曲线下的平均血浆浓度（AUC24（SIL + DMS））表示为625至13579 ng / h / ml。口服剂量为4.2 mg / kg / 24 h，成人AUC 24（SIL + DMS）的中位数为2650 ng / h / ml，相当于每天3次，每次20 mg。患者之间的差异很大，模拟的AUC 24（SIL + DMS）范围（第10和第90个百分位数）为1000-8000 ng / h / ml。结论：ECMO后新生儿和婴儿中SIL的药代动力学差异很大。在中位患者中，当前每天四次使用0.5-2.0 mg / kg的剂量方案导致的暴露量可与每天四次建议的成人剂量20 mg相媲美。仍然需要根据疗效和低血压的发生情况进行仔细的剂量滴定。后续研究应包括适当的药效学终点，并进行总体药代动力学/药效学分析以确定合适的暴露窗口或目标浓度。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号