PHARMACEUTICAL EXCIPIENTS - ADVERSE-EFFECTS ASSOCIATED WITH INACTIVE INGREDIENTS IN DRUG PRODUCTS .1.
PHARMACEUTICAL EXCIPIENTS - ADVERSE-EFFECTS ASSOCIATED WITH INACTIVE INGREDIENTS IN DRUG PRODUCTS .1.
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DOI：
10.1007/bf03259937
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发表时间：
1988-03-01
期刊：
影响因子：
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通讯作者：
RUMACK, BH
中科院分区：
文献类型：
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作者：
GOLIGHTLY, LK;SMOLINSKE, SS;RUMACK, BH
赋形剂反应的原因包括使用明显有毒的物质（例如二甘醇）、在易感人群中使用某些赋形剂（例如出生体重极低的新生儿、大面积烧伤患者、有哮喘或接触性皮炎病史的患者）、赋形剂混合物的改变导致生物利用度改变（例如苯妥英钠）以及故意或无意地硬膜外施用用于治疗的保存药物。静脉注射使用。当使用异常大剂量的含有防腐剂的药物时（吗啡中的氯丁醇，三硝酸甘油酯（硝化甘油）中的乙醇），也会发生无意的赋形剂过量。通过了解当前可用的配方，大多数赋形剂问题是可以预防的。政府药品监管机构在很大程度上阻止了新的有毒辅料的引入；然而，先前批准（但未充分研究）的赋形剂的新用途继续导致不幸的悲剧（例如E-ferol事件）。应仔细监测高危人群。极低出生体重婴儿（低于 WOg）对许多赋形剂有明显的不耐受性，特别是在出生后的前两周。研究应针对为该人群开发非防腐药物和更安全的稀释剂。先前已证明在其他人群中安全的药物和赋形剂（例如多沙普仑）应在建议广泛使用之前在该年龄组中进行仔细研究。哮喘患者是另一个对赋形剂毒性经常敏感的人群。在某些情况下，就像食品和药物中普遍存在的亚硫酸盐一样，完全避免可能是不可能的，预防性治疗可能是有益的。非活性成分显然在其生物活性方面并不总是惰性的，因此不应如此列出。一个更有用、更简洁的术语是赋形剂（excipient）。强烈建议所有药品制造商列出其所有辅料，并将其提供给从业人员和药物信息中心。或者或另外，包装说明书应根据良好的生产程序列出这些赋形剂。这一披露将有助于确定赋形剂在人群中可能出现的问题（生物等效性、毒性等）的相对频率和严重程度，并使易感患者能够避免无意中接触。
Excipient reactions have resulted from the use of clearly toxic substances (e.g. diethyleneglycol), the use of certain excipients in a susceptible group (e.g. very low birthweight neonates, patients with large surface area burns, patients with a history of asthma or contact dermatitis), the alteration of an excipient mixture resulting in altered bioavailability (e.g. phenytoin), and the deliberate or inadvertent extradural administration of preserved medications intended for intravenous use. Inadvertent excipient overdose has also occurred when unusually large doses of a drug containing a preservative were used [chlorbutol in morphine, ethanol in glyceryl trinitrate (nitroglycerin)].Most excipient problems are preventable with knowledge of the currently available formulation. Government drug regulatory agencies have largely prevented introduction of a new toxic excipient; however, the new use of previously approved (but not adequately studied) excipients continues to result in unfortunate tragedies (e.g. the E-ferol incident). Populations at risk should be monitored carefully. Very low birthweight infants (less than WOg) have a well-demonstrated intolerance to many excipients, particularly during the first 2 weeks of life. Research should be directed toward development of non-preserved medications and safer diluents for this population. Drugs and excipients which have previously been demonstrated to be safe in other populations (e.g. doxapram) should be meticulously studied in this age group before widespread use is recommended.Asthmatic patients comprise another population that are frequently sensitive to excipient toxicity. In some cases, as in sulphiting agents, which are ubiquitous in foods as well as in medications, total avoidance may not be possible and prophylactic therapy may be beneficial.Inactive ingredients are clearly not consistently inert in their biological activity and therefore should not be listed as such. A more useful and concise term is excipient. It is highly recommended that all pharmaceutical manufacturers list all their excipients and make this available to practitioners and drug information centres. Alternatively or additionally, the package insert should list these excipients in accordance with good manufacturing procedures. This disclpsure will help to determine the relative frequency and magnitude of problems (bioequivalence, toxicity, etc.) that excipients may have in the population, as well as enabling susceptible patients to avoid inadvertent exposure.