Short-term drug-drug interaction between sildenafil and bosentan under long-term use in patients with pulmonary arterial hypertension

• Material Type: 博士論文
• Title: Short-term drug-drug interaction between sildenafil and bosentan under long-term use in patients with pulmonary arterial hypertension
• Author/Editor: Miyakawa, Sachiko
• Author Heading: Miyakawa, Sachiko
• Publication, Distribution, etc.: Scientific Research Publishing
• Publication Date: 2013
• Publication Date (W3CDTF): 2013
• Alternative Title: 肺動脈性肺高血圧症患者における長期的なシルデナフィルとボセンタン使用下での両薬物の短期的薬物間相互作用
• Degree grantor/type: 浜松医科大学
• Date Granted: 2014-03-17
• Date Granted (W3CDTF): 2014-03-17
• Dissertation Number: 甲第672号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第672号
• Text Language Code: eng
• Subject Heading: Drug-Drug Interaction; Pulmonary Arterial Hypertension; Sildenafil; Bosentan; Pharmacokinetics
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; Sildenafil and bosentan are often co-administered for pulmonary arterial hypertension (PAH) treatment. The plasma concentration of sildenafil can be decreased by half if co-administered with bosentan. Many patients take these agents simultaneously in the morning and the evening. The aim of this study was to examine the pharmacokinetics of sildenafil which was interfered with bosentan administration to ascertain whether these agents should be given concomitantly or separately. A two-way crossover study was conducted in 6 PAH patients with combination therapy of sildenafil and bosentan. Participants underwent the sequence of treatment phases: phase S (sildenafil administered 3 h before bosen-tan); phase B (bosentan administered 3 h before sildenafil); and phase C (administered concomitantly). Blood samples were collected on the last day of each phase. There was no significant difference in maximum plasma concentration or area under the plasma concentration-time curve (AUC0-8) between phase C and phase S (95.5±24.8 vs. 72.9±40.9 (p=0.07), 209.7±81.8 vs. 180.2±126.4 (p=0.24), respectively) or between phases C and B (87.8±42.0 vs. 99.6±33.9 (p=0.59), 197.2±88.2 vs. 240.7±121.8 (p=0.19), respectively) (ng/mL, mean±standard deviation). Large intra- and inter-individual variability in sildenafil concentration was noted. The timing of administration of sildenafil and bosentan does not significantly influence the plasma concentration of sildenafil. Physicians do not need to be overly concerned about the timing of administration of these drugs to maximize the sildenafil concentration.
• DOI: info:doi/10.4236/pp.2013.47078; https://doi.org/info:doi/10.4236/pp.2013.47078
• Persistent ID (NDL): info:ndljp/pid/8953193; https://dl.ndl.go.jp/pid/8953193
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Available (W3CDTF): 2015-03-03
• Date Accepted (W3CDTF): 2015-02-03T05:25:05+09:00
• Date Created (W3CDTF): 2018-08-27
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/2783; https://hama-med.repo.nii.ac.jp/records/2651
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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