Pharmacokinetic analysis of new synthetic antimalarial N-251
国立国会図書館館内限定公開
収録元データベースで確認する
国立国会図書館デジタルコレクション
デジタルデータあり
公開元のウェブサイトで確認する
DOI[10.1186/s41182-019-0167-4]のデータに遷移します
全国の図書館の所蔵
国立国会図書館以外の全国の図書館の所蔵状況を表示します。
所蔵のある図書館から取寄せることが可能かなど、資料の利用方法は、ご自身が利用されるお近くの図書館へご相談ください
書誌情報
この資料の詳細や典拠（同じ主題の資料を指すキーワード、著者名）等を確認できます。
- 資料種別
- 記事
- 著者・編者
- Kazuaki OkadaAkira SatoAkiko Hiramoto
- 出版年月日等
- 2019-07-05
- 出版年（W3CDTF）
- 2019-07-05
- タイトル（掲載誌）
- Tropical medicine and health
- 巻号年月日等（掲載誌）
- 47(40)
- 掲載巻
- 47(40)
- ISSN（掲載誌）
- 1349-4147
- ISSN-L（掲載誌）
- 1348-8945
- 本文の言語コード
- eng
- DOI
- 10.1186/s41182-019-0167-4
- 国立国会図書館永続的識別子
- info:ndljp/pid/11377422
- コレクション（共通）
- コレクション（障害者向け資料：レベル1）
- コレクション（個別）
- 国立国会図書館デジタルコレクション > 電子書籍・電子雑誌 > その他
- 収集根拠
- オンライン資料収集制度
- 受理日（W3CDTF）
- 2019-10-28T20:45:15+09:00
- 保存日（W3CDTF）
- 2019-10-28
- 記録形式（IMT）
- application/pdf
- オンライン閲覧公開範囲
- 国立国会図書館内限定公開
- デジタル化資料送信
- 図書館・個人送信対象外
- 遠隔複写可否（NDL）
- 可
- 掲載誌（国立国会図書館永続的識別子）
- info:ndljp/pid/11285294
- 連携機関・データベース
- 国立国会図書館 : 国立国会図書館デジタルコレクション
- 要約等
- Background<br> With the emergence and growing number of drug-resistant Plasmodium falciparum, a new drug for malaria control must be urgently developed. The new antimalarial synthetic compound N-251 was recently discovered. As an endoperoxide structure in the body, the compound shows high antimalarial activity and curative effects. We performed a pharmacokinetic (PK) analysis of N-251 under various conditions using mice to understand the inhibitory effect of N-251 in parasite-infected mice.<br> <br> Results<br> PK study of N-251 after intravenous and oral administration in mice showed plasma concentration of N-251 was decreased drastically by intravenous route. Cmax was reached in 2 h after oral administration of N-251, and the level decreased to a level similar to that obtained after intravenous administration. The area under the curves (AUCs) of the plasma concentration of N-251 increased dose-proportionally in both administrations, and bioavailability (F) was approximately 23%. Additionally, Tmax, Cmax, AUC, and F increased in fasted mice compared to normal-fed mice after the administration of N-251, indicating the influence of diet on the absorption kinetics of N-251. Furthermore, in parasite-infected fasted mice, the plasma concentration-time profile of N-251 was similar to that in normal-fasted mice. Based on the PK parameters of single oral administration of N-251, we investigated the effect of multiple oral doses of N-251 (68 mg/kg three times per day for 2 days) in normal-fed mice. The plasma concentration of N-251 was between 10 and 1000 ng/mL. The simulation curve calculated based on the PK parameters obtained from the single-dose study well described the plasma concentrations after multiple oral dosing, indicating that N-251 did not accumulate in the mice. Multiple oral administrations of N-251 in mice were required to completely eliminate parasites without accumulation of N-251.<br> <br> Conclusions<br> N-251 has been selected as a potent antimalarial candidate. We found that N-251 showed short half-life in plasma, and AUCs increased proportionally to dose. With multiple doses of N-251, the plasma level of N-251 was greater than 10 ng/mL in normal-fed mice, and accumulation of N-251 was not observed; however, multiple treatments with N-251 are required for the complete cure of parasite-infected mice. Determining the appropriate dosage was an important step in the clinical applications of N-251.
- DOI
- 10.1186/s41182-019-0167-4
- オンライン閲覧公開範囲
- インターネット公開
- 著作権情報
- © The Author(s).
- 関連情報（URI）
- 参照
- Evaluating the activity of N-89 as an oral antimalarial drug
- 参照
- Accumulation of artemisinin trioxane derivatives within neutral lipids of Plasmodium falciparum malaria parasites is endoperoxide-dependentSynthesis and Antimalarial Activity of Cyclic Peroxides, 1,2,4,5,7-Pentoxocanes and 1,2,4,5-Tetroxanes<i>Plasmodium falciparum</i> Endoplasmic Reticulum-Resident Calcium Binding Protein Is a Possible Target of Synthetic Antimalarial Endoperoxides, N-89 and N-251<i>Qinghaosu</i> (Artemisinin): an Antimalarial Drug from ChinaIdentification of an endoplasmic reticulum-resident calcium-binding protein with multiple EF-hand motifs in asexual stages of Plasmodium falciparum1Note: Nucleotide sequence data reported in this paper have been deposited in the GenBank™ data base with the accession number AF016410.1Impact of chrysosplenetin on the pharmacokinetics and anti-malarial efficacy of artemisinin against Plasmodium berghei as well as in vitro CYP450 enzymatic activities in rat liver microsomeAntimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-olStage specific activity of synthetic antimalarial endoperoxides, N-89 and N-251, against Plasmodium falciparumThe global distribution of clinical episodes of Plasmodium falciparum malariaEvaluation of in vivo dissolution behavior and GI transit of griseofulvin, a BCS class II drugEvidence of Artemisinin-Resistant Malaria in Western CambodiaState‐of‐the‐Art Clinical Article: Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and MenEmergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal studyQinghaosu (Artemisinin): The Price of SuccessSynthesis and Antimalarial Activity of Novel Medium-Sized 1,2,4,5-TetraoxacycloalkanesThe Threat of Artemisinin-Resistant MalariaArtemisinin Resistance in <i>Plasmodium falciparum</i> MalariaMedical need, scientific opportunity and the drive for antimalarial drugsA pharmacokinetics analysis program (MULTI) for microcomputer
- 連携機関・データベース
- 国立情報学研究所 : CiNii Research
- 提供元機関・データベース
- 学術機関リポジトリデータベース雑誌記事索引データベースCrossref科学研究費助成事業データベースCrossref
- 書誌ID（NDLBibID）
- 11377422