目的 通过对61种常用皮肤外用药物的处方集及说明书进行调查,掌握目前皮肤外用药物关于妊娠期应用的明确阐述,同时对于37种非禁用或避免使用的药物透皮能力及其中30种已知动物毒性数据进行评估,以期为妊娠期妇女的临床皮肤用药提供定性及定量的药学参考。方法 分类分析皮肤外用药物处方集及说明书关于妊娠期用药的表述,对于非禁用或避免使用的药物,采用ACD/LAB 6.0 计算药物的logP、logD、MW,通过Potts-Guy模拟方程评估其透皮能力,采用TOXNET数据库查询药物的动物毒性实验,通过不同种属体表面积换算,估算皮肤外用药物的妊娠危险剂量。结果 目前处方集及说明书表述中禁用16种,不推荐/避免/不宜使用的共8种,慎用/权衡利弊共14种,在医师指导下使用的共7种,尚不明确或无明确表述的共16种,非禁用或避免使用的药物中,有9种药物logKp大于-5,透皮能力最强的为布替萘芬和舍他康唑, pH 5.5和pH 7.0条件下各有7种药物透皮能力logK′p值较未解离状态logKp值降低,其透皮能力受pH影响较大,15种药物透皮能力不受pH的影响。37种非禁用或避免使用的药物中7种药物无动物实验数据,14种药物妊娠危险人体等效剂量在10 mgkg-1以下。结论 目前皮肤外用药物关于妊娠期用药的处方集及说明书表述明确的药物有限,通过药物自身理化性质及动物毒性实验可为皮肤外用药物临床应用提供定性及定量的药学支持。
Abstract
OBJECTIVE The aim of this study is to investigate labelings on dermatologic drugs for pregnant women and provide qualitative and quantitative pharmaceutical support for clinical use. METHODS Labelings and formularies on pregnancy of topical drugs were analyzed and sorted according to classification on pregnancy use. Transdermal abilities of the drugs not forbidden nor avoided were evaluated through ACD/LAB 6.0 software and Potts-Guy formulation. Through TOXNET database and dose conversion equation, toxicities on animals were collected and human doses for pregnant women were calculated. RESULTS In dermatologic drugs, there are 16 drugs forbidden, 8 not recommended/avoided/should not be used, 14 used with caution/weighed pros and cons, 7 used under instruction, 16 unclear or with no statement. In topical drugs not forbidden nor avoided, there are 9 drugs′ logKp above-5, butenafine and sertaconazole with strongest transdermal abilities, 7 drugs′ logKp influenced under pH5.5 or pH7.0, with a decline in logK′p compared with logKp, still 15 drugs not influenced by pH, 7 drugs′ toxicities on animals unknown, 14 drugs′ pregnancy human doses under 10 mgkg-1. CONCLUSION Currently,only a few topical drugs′ instructions on pregnancy are clear. With properties and animal experiments, better pharmaceutical support can be provided for clinical use on qualitative or quantitative reference.
关键词
妊娠期 /
皮肤外用药物 /
处方集 /
说明书 /
用药策略
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Key words
pregnancy /
dermatologic drug /
formulary /
labeling /
drug strategy
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中图分类号：
R969.3
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参考文献
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脚注
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基金
G20工程支撑保障十病十药研发项目资助(Z151100003815016)
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