儿科用药中临时配制液体制剂的应用现状

儿童和成人的生理特点等方面存在很大不同,儿科用药剂量不能简单地通过成人剂量来计算,且普通的分剂量操作存在很多问题,因此需要通过临时配制液体制剂来改善这一问题。国外已有临时配制溶媒商品上市使用,但目前国内还没有此类商品。本文主要概述国内儿科用药分剂量的现状,以及国外部分国家临时配制的商品和所制定的法规及标准,旨在为临时配制液体制剂提供新思路,改善儿科用药的部分问题。     

国内利巴韦林制剂说明书存在的问题

目的:了解国内不同厂家、不同制剂利巴韦林药品说明书内容的差异,为促进临床合理用药和规范利巴韦林药品说明书提供依据。方法:对37份国内利巴韦林制剂药品说明书进行调查分析。结果:部分说明书在孕妇用药、儿童用药、成人用药剂量上存在问题,注射液说明书存在静脉滴注浓度不一的问题。结论:国内利巴韦林制剂说明书的内容有待完善,建议药品监督管理部门加强对药品说明书的安全监管,保障公众用药安全。     

儿科临时调配口服制剂发展现状

儿童不是成人的缩小版。国内外普遍缺乏适合儿科人群的药物剂型和规格，导致现阶段分剂量用药不可避免。临时调配口服制剂属于分剂量用药的一种，具有显著的优点，适合各年龄段的儿科人群。本文概述了目前儿童分剂量用药的现状，介绍了临时调配口服制剂的特点和潜在风险点，以及国外针对临时调配口服制剂的法律规范和实践经验，旨在为中国确立临时调配制剂的合法地位，建立相应的技术标准和管理模式提供参考。     

某三级妇幼专科医院儿科常用药品调查分析

目的:了解儿童用药现状,保障儿童用药安全。方法:调查某三级妇幼专科医院门诊处方20 320张,统计处方中的常用药品,分析比较其药品剂型、医保类型和药品说明书等情况。结果: 20 320张处方中共涉及药品145种,其中儿童用制剂60种(41.38%),成人用制剂85种(58.62%);85种成人用制剂中有78种(91.76%) 纳入医保报销,而儿童用制剂仅有34种(56.67%)被纳入医保目录。在所涉及到145种药品中,提及儿童用药信息的有133种(91.72%),但仅有86种(59.31%)标明了儿科用法用量,标明了新生儿剂量的只有13种(8.97%)。结论:某三级妇幼专科医院儿童用制剂配备不足,药品说明书儿童用药信息不全,反映出我国儿科医疗资源的匮乏,亟需制定相应的政策,以确保儿童用药的安全性和依从性。     

口服固体制剂精准分剂量在精准用药中的探索与实践

目的:为医院口服固体制剂的使用提供一种精准分剂量方法,为临床合理用药提供参考。方法:利用药片切割器、药片磨粉器等对口服固体制剂进行分劈、磨粉或胶囊内容物直接分装,并称重进行调整,以保证分剂量准确度控制在均分量的85%~115%以内。结果:提供药品精准分剂量服务,能够保证分剂量准确度,提高用药安全性、有效性和方便性,减少药品浪费,降低用药成本。结论:医院药学部门开展药品精准分剂量是精准用药的现实基础,使医院药学服务更加精细,提高患者用药依从性,医护患满意,值得推广。     

片剂分剂量临床现状分析与探讨

片剂分剂量是临床常用的调整药物剂量方法,其准确度及稳定性直接关系药品质量,影响临床用药的安全性及有效性。然而,目前国内对于片剂分剂量的质量管理规章制度缺失,对片剂分剂量长期一直延续着无质量监管要求的传统模式,这也导致了片剂分剂量在满足个体化用药需求的同时存在潜在用药风险。本文通过参阅国内外片剂分剂量法规及文献,从目前国内外片剂分剂量现状、片剂分剂量现存问题、降低片剂分剂量风险策略三方面入手进行文献综述,以期引起相关管理部门的重视,最大限度保障患者用药安全。     

国内外儿童用药个性化制剂发展与思考

通过文献分析，搜索现有的国内外儿童个性化制剂，分析儿童用药个性化制剂发展现状、特点及应用，为我国开发出适宜儿童使用的个性化制剂提供参考。结果表明，目前我国常用的儿童个性化制剂主要指分剂量调剂和临时配制液体制剂两种类型，但这种未经许可的药物使用存在着诸多问题。国外儿童个性化制剂主要指配置制剂和3D打印两种类型，并开发了多种个体化剂型和技术。我国可通过借鉴国外个性化制剂发展，改善相关法律政策、开发多功能辅料、加强药师操作培训等，促进我国儿童用药个性化制剂发展。     

品管圈提高儿童口服片剂分剂量准确率的实践与探索

目的：提高儿童口服片剂分剂量的准确率,保障临床用药的安全性与有效性。方法：基于品管圈活动,分析探索存在的问题与可行的改进措施,采用PDCA循环流程,通过比较分析品管圈活动前后片剂分剂量的准确率评价改进方法并制订规范化作业书。结果：分剂量过小和操作不规范是导致儿童口服片剂分剂量差错的主要原因,采用磨粉分装与规范化操作培训考核后,分剂量准确率由80.0%提高至95.0%。结论：开展品管圈活动可以解决分剂量准确率较低的问题,通过磨粉分装与规范化操作培训考核可以提高儿童口服片剂分剂量的准确率,保障临床用药的安全性与有效性。     

儿科药品分剂量现状浅析

目的:通过分析目前儿科药品分剂量的方法,评价儿科药品分剂量现状。方法:参考文献,对儿科药品片剂分剂量方法,颗粒剂、胶囊剂等固体制剂分剂量方法,注射液等液体制剂分剂量方法进行分析、评价。结果:片剂分剂量为1/2、1/4片时适合双手对掰法或使用药片切割器,分剂量为1/3、1/5片等难以均分的等份时,适合磨粉分剂量法或固体药品液体化法,但需具体考虑药品的理化性质;颗粒剂、胶囊剂等固体制剂分剂量的方法多采用目测估计法、固体药品液体化法等;注射液等液体制剂分剂量的方法多会造成浪费,特别需要注意剂量与体积的换算,且分剂量准确性与取样量和量具有关。结论:将成人药品分剂量用于儿童存在安全隐患,建议国家制定相应政策,鼓励制药企业加大儿童专用药品的研发力度,从而减少药品分剂量可能引发的风险。     

儿科医院中成药的应用状况调查

目的通过对医院中成药品种和使用的调查,了解临床儿童使用中成药的现状。方法统计临床使用中成药的种类,儿童用中成药的品种数、剂型、作用类别等,调查中成药说明书中儿童用药的相关提示。随机抽样调查和分析医院患儿中成药治疗的状况。结果医院中成药在治疗儿童疾病方面日益多元化,但儿童专用的中药制剂仍非常少,且主要为呼吸系统用药和消化系统用药。在儿科使用的成人中药,对儿童用药缺乏剂量和用药指导,儿童用药安全性也不明确。结论儿童中药制剂仍较匮乏,亟待研究开发更多的儿童中药制剂,丰富中药的儿童用药资料。     

Harmful excipients in medicines for neonates in Spain

Background Neonates may respond differently from adults to drug components. Hence, ingredients that seem safe in adults may not be safe in this age group. Objective To describe the content of harmful excipients in drugs used in our neonatal wards and compare the daily dose a neonate may receive with the accepted daily intake (ADI) in adults. Methods All drugs included in the hospital’s neonatal treatment guide were reviewed, using information from the package inserts or the summary of product characteristics. Those containing at least one harmful excipient (e.g., metabisulfite, sorbitol) were analyzed. Minimum and maximum usual daily drug doses were determined, and excipient exposure was estimated by extrapolation of the minimum and maximum of excipient referred to the active ingredient. These amounts were compared with ADIs for each excipient in adults. Results In total, 32 % of intravenous and 62 % of oral formulations used in neonates contained at least one harmful excipient. On quantitative analysis, 25 % of intravenous and 19 % of oral drugs contained harmful excipients exceeding the ADI in adults. Conclusion Several drugs commonly used to treat neonates contain harmful excipients in amounts that may exceed the ADI in adults. Clinicians should be aware of this to prescribe appropriate treatment in this population.     

Treating disorders of the neonatal central nervous system: pharmacokinetic and pharmacodynamic considerations with a focus on antiepileptics

A major consideration in the treatment of neonatal disorders is that the selected drug, dose and dosage frequency is safe, effective and appropriate for the intended patient population. Thus, a thorough knowledge of the pharmacokinetics and pharmacodynamics of the chosen drug within the patient population is essential. In paediatric and neonatal populations two additional challenges can often complicate drug treatment – the inherently greater physiological variability, and a lack of robust clinical evidence of therapeutic range. There has traditionally been an overreliance in paediatric medicine on extrapolating doses from adult values by adjusting for bodyweight or body surface area, but many other sources of variability exist which complicate the choice of dose in neonates. The lack of reliable drug dosage data in neonates has been highlighted by regulatory authorities, as only ~50% of the most commonly used paediatric medicines have been examined in a paediatric population. Moreover, there is a paucity of information on the pharmacokinetic parameters which affect drug concentrations in different body tissues, and pharmacodynamic responses to drugs in the neonate. Thus, in the present review, we draw attention to the main pharmacokinetic factors that influence the unbound brain concentration of neuroactive drugs. Moreover, the pharmacodynamic differences between neonates and adults that affect the activity of centrally‐acting therapeutic agents are briefly examined, with a particular emphasis on antiepileptic drugs.     

Failure of neonatal injection of hexachlorophene to affect reproduction in hamsters

Neonatal administration of a near lethal dose of hexachlorophene had no effect on time of puberty, estrous cycle regularity, fertility, or body weight in hamsters (Mesocricetus auratus). This indicates that the drug does not interfere with neonatal sexual differentiation of the hypothalamic center that later controls pituitary gonadotropin release in adults.     

Prenatal and neonatal drug metabolism in man

Summary Drug oxidations are catalyzed by the liver microsomal fraction of human fetuses but not by fetal livers from most experimental animals. In contrast, glucuronidation of some substrates is catalyzed by the rat fetal liver in late gestation but not in the human fetal liver. The deficient human fetal glucuronidation seems to be compensated for by early development of sulfation activity. The inconsistency of the results from animal fetuses and human fetuses shows that animal data have little relevance for the human fetus. No generalized statements can be made about drug disposition in the newborn infant as compared to adults. Although most drugs that are oxidized have prolonged plasma half-lives in the neonatal period there are examples of drugs with half-lives similar to, or even shorter than, the average half-lives in adults. Oxazepam is conjugated with glucuronic acid in adults. The neonatal plasma half-life of this drug is considerably prolonged. This is true also for its conjugate as would be expected from the immature renal function in newborns. Adequate pharmacokinetic information is a prerequisite for rational and safe drug treatment in the neonatal period.Presented at the International Workshop on Perinatal and Pediatric Aspects of Clinical Pharmacology, Heidelberg, Federal Republic of Germany, 27–29 February 1980     

Analysis of anti-infection therapeutic schedule analysis for neonatal Streptococcus agalactiae meningitis and discussion on the indications for drug withdrawal

The clinical manifestations of neonatal GBS meningitis are as follows: non-specificity, long hospital stay, easy to cause neurological complications, and sequelae. Clinical pharmacist participated in the anti-infective treatment of a neonatal Streptococcus agalactiae meningitis whose cerebrospinal fluid was still abnormal when the drug was stopped. According to the PK/PD characteristics of antibacterial drugs, the permeability of the blood-brain barrier, and the adjustment of the antibiotic dose, the reasons for the decrease in the number of cerebrospinal fluid cells after vancomycin treatment were analyzed. Clinical pharmacists also analyzed the efficacy of linezolid in the treatment of neonatal bacterial meningitis, and discussed the indications for stopping medication when the cerebrospinal fluid is abnormal, so as to improve the safety and effectiveness of antibiotics in the treatment of neonatal bacterial meningitis.     

Pediatric Dose Selection and Utility of PBPK in Determining Dose

Interest in determining safe and efficacious doses for drug administration in pediatric patients has increased dramatically in recent years. However, published pediatric clinical studies have failed to increase proportionally with adult clinical study publications. In order to assess the current state of pediatric dose determination and the supporting role of physiologically based pharmacokinetic modeling and simulation in determining pediatric dose, the pediatric clinical literature (2006–2016) and case examples of pediatric PBPK modeling efforts were reviewed. The objective of this assessment was to investigate the contribution of PBPK to our understanding of the differences between children and adults, which lead to differences in drug dose. Pediatric and adult dose data were available for 31 small molecule drugs. In general, pediatric dose was well-correlated with adult data, with an apparent tendency for higher body weight- or body surface area-normalized pediatric dose. Overall performance of pediatric PBPK modeling approaches was considered to adequately predict observed data. However, model performance was dependent upon age group simulated, with approximately half of neonatal predictions falling outside of 1.5-fold of observed. In conclusion, there is a clear need for further refinement of starting dose in pediatric phase 1 studies, and utilization of PBPK could lead to reduced numbers of patients required to establish safe and efficacious doses in the pediatric population.     

儿童中常见的药物不良反应

病人特别是儿童常发生药物不良反应,在新生儿监护室中发生的不良反应高达30％。甲氧氟普胺引起的肌张力障碍,抗惊厥药引起嗜睡,氯霉素引起灰婴综合征以及皮质类固醉造成的发育障碍都可在儿童中出现。药物有关不良反应在儿童中发生率比成人高的主要原因可能是儿童代谢功能不成熟之故。     

某妇产医院新生儿重症医学科用药特征分析

[摘要]目的：探讨新生儿重症监护病房（NICU）的用药特点、用药问题及影响新生儿药物暴露的因素,从而促进NICU的合理用药和药学监护。方法：随机抽取400例NICU患儿,分析患儿围产期临床特征、人口学特征和药物治疗情况。对患儿用药数量与围产期临床和人口学特征进行单因素分析及相关分析。结果：400例患儿胎龄38.50（4.00）周,用药数量5.00（3.00）种。患儿使用的药物数量与胎龄、出生体质量、Apgar评分呈负相关,与住院时间和机械通气时间呈正相关。常用药物主要为维生素类、营养类药物、酶制剂、调节水、电解质和酸碱平衡的药物、抗感染药物、消化系统药物、血液及造血系统药物、中枢神经系统药物、泌尿和生殖系统药物和中药清热剂。使用的79种药品中65种包含儿童用药信息,27种包含新生儿用药信息,12种仅有成人用药信息。结论：NICU中胎龄低、出生体质量低、住院时间长、机械通气时间长、Apgar评分低、并发症多的患儿,用药数量多,应重点进行药学监护;新生儿常用药品说明书信息短缺,可通过减少辅助用药的使用促进新生儿合理用药。     

新生儿败血症112临床分析

目的：探讨新生儿败血症的临床表现、病原菌特点及治疗方案。方法：对112例新生儿败血症患儿的临床资料进行研究分析。结果：新生儿败血症按发病机制分为早发型（占29．5％）、晚发型（占63．4％）及院内获得型（占7．1％）。以皮肤（占47．1％）、脐部（占46．3％）、呼吸道（占43．2％）为主要感染途径,病原菌以葡萄球菌为主（占75．0％）,临床表现多样,缺乏特异性,经综合治疗大多预后良好。结论：新生儿败血症临床表现缺乏特异性,早期诊断,早期治疗,根据药敏实验选用合理抗生素是治疗成败的关键,加强皮肤,脐部等处护理．无菌操作可减少其发病率。     

全凭静脉麻醉下持续输注国产阿曲库铵的药效学观察

目的:探讨持续输注国产阿曲库铵的可行性及平均输注速率,检测验证其临床效价。方法:择期手术患者80例,采用全凭静脉麻醉,肌松监测下(TOF)国产阿曲库铵0.5mg/kg诱导插管,术中调整持续输注速率以维持T1于对照值的1%～10%,术毕前20min停止输注。结果:平均输注速率(5.1±0.4)(μg·kg)/min,起效时间(203±47)s,临床作用时间(41.5±4.5)min;TOF无反应期PTC与T1首次出现时间之间及拔管时TR值与DBS值之间均显著相关(P<0.001);恢复指数(14.9±3.7)min,停药到拔管时间(44.1±6.1)min。结论:在肌松监测下,持续输注国产阿曲库铵不但可为手术提供稳定的、可控的肌肉松弛,而且输注停止后,神经肌肉传递功能恢复迅速而完全。