Investigation of the Safety of Topical Metronidazole from a Pharmacokinetic Perspective
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- Iida Junichi
- Research Institute of Pharmaceutical Sciences, Musashino University Department of Pharmacy, Saiseikai Yokohamashi Nanbu Hospital
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- Kudo Toshiyuki
- Research Institute of Pharmaceutical Sciences, Musashino University
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- Shimada Kento
- Research Institute of Pharmaceutical Sciences, Musashino University
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- Yatsuno Yoshiyuki
- Research Institute of Pharmaceutical Sciences, Musashino University
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- Yamagishi Saori
- Research Institute of Pharmaceutical Sciences, Musashino University
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- Hasegawa Satoshi
- Department of Surgery, Saiseikai Yokohamashi Nanbu Hospital
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- Ike Hideyuki
- Department of Surgery, Saiseikai Yokohamashi Nanbu Hospital
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- Sato Toru
- Department of Pharmacy, Saiseikai Yokohamashi Nanbu Hospital
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- Kagaya Hajime
- Department of Pharmacy, Saiseikai Yokohamashi Nanbu Hospital
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- Ito Kiyomi
- Research Institute of Pharmaceutical Sciences, Musashino University
この論文をさがす
抄録
Metronidazole (MTZ) ointment has been used widely as a hospital preparation against cancerous malodor. Although cancerous tissue with ulcer-like symptoms is likely to have a higher capacity to absorb drugs than normal skin, the extent to which MTZ is absorbed when a topical preparation is applied to cancerous tissue remains unclear. Furthermore, few studies have investigated the drug interactions involving MTZ despite its long use in clinical practice. In the present study, plasma concentration of MTZ was measured in a breast cancer patient using MTZ ointment for cancerous malodor and basic research was also conducted with the objective of investigating the safety of topical MTZ from a pharmacokinetic perspective. 4.75 µg/mL (27.8 µM) of MTZ was detected in the patient’s plasma, which was close to the plasma concentration after oral dosage of MTZ. In a metabolic inhibition study using human liver microsomes, cytochrome P450 (CYP) 2C9-mediated hydroxylation of S-warfarin was almost unaffected by MTZ at the corresponding concentrations. In addition, 3-d repeated oral administration of MTZ (200 mg/kg/d) to rats did not show any significant effects on the hepatic mRNA levels of various CYP isozymes and CYP2C protein levels. These results suggest that the reported interaction of oral MTZ and S-warfarin was not due to CYP2C9 inhibition and that drug interactions via inhibition of CYP2C9 is unlikely to occur when MTZ ointment is applied to ulcerous skin. This information should be valuable for assessing the safety of MTZ ointment used for mitigating cancerous malodor.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 36 (1), 89-95, 2013
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204633305600
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- NII論文ID
- 130003361351
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3s3otFahsA%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024173516
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- PubMed
- 23302640
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可