目的 阐述我国某三级甲等教学医院新生儿重症监护室中新生儿药用辅料暴露情况。方法 回顾性收集2017年新生儿重症监护室患儿的基本信息和药品,分析统计辅料涉及的药品、暴露人数和暴露医嘱次数。结果 纳入627例患儿的共17 640份医嘱,共涉及238个药品,其中55.5%药品说明书中明确辅料成分,涉及辅料共171种,以注射用水、氯化钠和氢氧化钠为最常见。有害辅料共涉及16个药品(6.7%),以丙二醇涉及药品种类最多。人群中暴露百分比最高的有害辅料是丙二醇(90.4%),其次为对羟基苯甲酸甲酯(84.7%)和聚山梨酯80(82.1%)。从医嘱中分析,暴露次数最多的是对羟基苯甲酸甲酯,其次是丙二醇和聚山梨酯80。在不同出生体重新生儿中丙二醇、对羟基苯甲酸甲酯、聚山梨酯80和乙醇的暴露人数百分比无显著差异。结论 新生儿重症监护室患儿中有害辅料暴露比例高,有害辅料的日暴露量和累积暴露量有待进一步研究。
Abstract
OBJECTIVE To describe the exposure to the excipients in the neonatal intensive care unit of a class A teaching hospital in China. METHODS A prospective cross-sectional study recorded all neonates in neonatal intensive care unit in 2017. The following information was extracted from the hospital medical records: demographic data and prescriptions for all drugs. RESULTS A total of 627 subjects with 17 640 prescriptions were collected. Water for injection was the most common excipient,followed by sodium chloride and sodium hydroxide. Sixteen of 238 drugs (6.7%) were involved in harmful excipients and propylene glycol was the most common harmful excipient in these drugs. Propylene glycol, methylparaben and polysorbate 80 were the three most common harmful excipients exposed to 90.4%, 84.7%, and 82.1% of neonates, respectively. Methylparaben was the most prescribed harmful excipient in medication orders, followed by propylene glycol and polysorbate 80. There was no significant difference of the exposure rate of harmful excipients among infants with different birth weights. CONCLUSION Harmful excipients exposures are common among neonates in neonatal intensive care unit. Future researches should evaluate the daily dose and cumulative dose of harmful excipients.
关键词
药用辅料 /
新生儿重症监护室 /
新生儿 /
早产儿
{{custom_keyword}} /
Key words
excipient /
neonatal intensive care unit /
neonate /
premature infant
{{custom_keyword}} /
中图分类号:
R969.3
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] INTERNATIONAL PHARMACEUTICAL EXCIPIENT COUNCIL. IPEC General Glossary of Terms and Acronyms-Updated (Version 2) [EB/OL]. [2021-2-10]. https://ipec-federation.org/wp-content/uploads/ 2021/02/2021-02-10-IPEC-General-Glossary-of-Terms-and-Acronyms-FINAL.pdf.
[2] WEINER M L, KOTKOSKIE L A. Excipient Toxicity and Safety [M]. 1st Ed. Boca Raton: CRC Press, 1999.
[3] EUROPEAN MEDICINES AGENCY. Excipients in the label and package leaflet of medicinal products for human use (Revision 1) [EB/OL]. [2019-11-22]. https://www.ema.europa.eu/en/documents/scientific-guideline/annex-european-commission-guideline-excipients-labelling-package-leaflet-medicinal-products-human_en.pdf.
[4] NATIONAL MEDICAL PRODUCTS ADMINISTRATION. Announcement of the national medical products administration on improving approval and supervision related on drug review(NO.56 in 2019) [EB/OL]. [2019-7-15]. http://www.gov.cn/gongbao/content/2019/content_5442292.htm.
[5] CHEN L,SONG Z H, HU S J, et al. An introduction to the standards system and main characteristics of pharmaceutical excipients in the 2020 Edition of Chinese Pharmacopoeia[J]. Chin Pharm J(中国药学杂志), 2020, 55(14):1177-1183.
[6] KEARNS G L, ABDEL-RAHMAN S M, ALANDER S W, et al. Developmental pharmacology--drug disposition, action, and therapy in infants and children[J]. N Engl J Med, 2003, 349(12):1157-1167.
[7] GINSBERG G, HATTIS D, SONAWANE B. Incorporating pharmacokinetic differences between children and adults in assessing children's risks to environmental toxicants[J]. Toxicol App Pharmacol, 2004, 198(2):164-183.
[8] ALLEGAERT K, VAN DE VELDE M, VAN DEN ANKER J. Neonatal clinical pharmacology[J]. Paediatr Anaesth, 2014, 24(1):30-38.
[9] FABIANO V, MAMELI C, ZUCCOTTI G V. Paediatric pharmacology: remember the excipients[J]. Pharmacol Res, 2011, 63(5):362-365.
[10] GARCIA-PALOP B, MOVILLA POLANCO E, CAÑETE RAMIREZ C, et al. Harmful excipients in medicinesfor neonates in Spain[J]. Int J Clin Pharm, 2016, 38(2):238-242.
[11] DE SOUZA A S, JR, DOS SANTOS D B, REY L C, et al. Off-label use and harmful potential of drugs in a NICU in Brazil: a descriptive study[J]. BMC Pediatr, 2016, 16(1):13.
[12] NELLIS G, METSVAHT T, VARENDI H, et al. Potentially harmful excipients in neonatal medicines: a pan-European observational study[J]. Arch Dis Child, 2015, 100(7):694-699.
[13] FISTER P, URH S, KARNER A, et al. The prevalence and pattern of pharmaceutical and excipient exposure in a neonatal unit in Slovenia[J]. J Matern Fetal Neonatal Med, 2015, 28(17):2053-2061.
[14] VALEUR K S, HERTEL S A, LUNDSTRØM K E, et al. The cumulative daily tolerance levels of potentially toxic excipients ethanol and propylene glycol are commonly exceeded in neonates and infants[J]. Basic Clin Pharmacol Toxicol, 2018, 122(5):523-530.
[15] LASS J, NAELAPÄÄ K, SHAH U, et al. Hospitalised neonates in Estonia commonly receive potentially harmful excipients[J]. BMC Pediatr, 2012, 12(8):136.
[16] FEUDTNER C, CHRISTAKIS D A, CONNELL F A. Pediatric deaths attributable to complex chronic conditions: a population-based study of Washington State, 1980-1997[J]. Pediatr, 2000, 106(1 Pt 2):205-209.
[17] FEUDTNER C, FEINSTEIN J A, ZHONG W, et al. Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation[J]. BMC Pediatr, 2014, 14(8):199.
[18] SALUNKE S, BRANDYS B, GIACOIA G, et al. The STEP (safety and toxicity of excipients for paediatrics) database: part 2-the pilot version[J]. Int J Pharm, 2013, 457(1):310-322.
[19] THEBAUD B, GOSS K N, LAUGHON M, et al. Bronchopulmonary dysplasia[J]. Nat Rev Dis Primers, 2019, 5(1):78.
[20] ASCHNER J L, BANCALARI E H, MCEVOY C T. Can We Prevent Bronchopulmonary Dysplasia?[J]. J Pediatr, 2017, 189(10):26-30.
[21] HEYMAN M B, COMMITTEE ON N. Lactose intolerance in infants, children, and adolescents[J]. Pediatrs, 2006, 118(3):1279-1286.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金项目资助(81773819);浙江省自然科学基金项目资助(Y16H160129)
{{custom_fund}}