Christensen R D, Alder S C, Richards S C, Horn J T, Lambert D K, Baer V L
Department of Women and Newborn, Intermountain Health Care and the McKay-Dee Hospital Center, Ogden, UT 84403, USA.
J Perinatol. 2006 Feb;26(2):120-4. doi: 10.1038/sj.jp.7211440.
We enterally administered a 14-day course of 3-mercapto-D-valine (D-penicillamine) to five extremely low birth weight (ELBW) neonates, as a step toward assessing this therapy as a means of reducing the incidence or severity of retinopathy of prematurity (ROP).
The study drug (100 mg/ml) was given by nasogastric tube at a dose of 100 mg/k every 8 h for three days, and then 50 mg/k once per day for 11 additional days. Logbooks were maintained by the bedside nurses to record signs of possible immediate intolerance. Laboratory tests assessed hepatic, renal, and hematologic toxicity. ROP was scored according to the ICROP guidelines. Comparisons were with a cohort of 139 consecutive recent neonates of the same birth weight and gestational age range.
Five neonates were enrolled in the study, and all received the full course of study drug as planned. Signs of immediate intolerance of the study drug were not observed in any. The study patients did not have a higher incidence, than that of the cohort group, in creatinine elevation, thrombocytopenia, neutropenia, hyperbilirubinemia, or abnormal liver function test. Four of the five had no ROP and one developed transient stage 1, compared with a 54% occurrence of ROP in the cohort.
It is feasible to enterally administer a 14-day course of 3-mercapto-D-valine to ELBW neonates and the suspension appears to be well tolerated. These results suggest that phase II safety and preliminary efficacy trials can be undertaken.
我们对5名极低出生体重（ELBW）新生儿进行了为期14天的3-巯基-D-缬氨酸（D-青霉胺）肠内给药，作为评估该疗法作为降低早产儿视网膜病变（ROP）发生率或严重程度手段的第一步。
研究药物（100mg/ml）通过鼻胃管给药，剂量为每8小时100mg/kg，持续3天，然后每天一次50mg/kg，持续11天。床边护士记录日志以记录可能的即刻不耐受迹象。实验室检查评估肝、肾和血液学毒性。ROP根据ICROP指南进行评分。与一组139名近期出生体重和胎龄范围相同的连续新生儿进行比较。
5名新生儿纳入研究，均按计划接受了完整疗程的研究药物。未观察到任何对研究药物的即刻不耐受迹象。研究患者在肌酐升高、血小板减少、中性粒细胞减少、高胆红素血症或肝功能检查异常方面的发生率并不高于队列组。5名患者中有4名没有ROP，1名发展为短暂的1期，而队列中ROP的发生率为54%。
对ELBW新生儿进行为期14天的3-巯基-D-缬氨酸肠内给药是可行的，该混悬液似乎耐受性良好。这些结果表明可以进行II期安全性和初步疗效试验。
