JP5523552B2 - 薬物動態を改善する方法 - Google Patents
薬物動態を改善する方法 Download PDFInfo
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- JP5523552B2 JP5523552B2 JP2012506491A JP2012506491A JP5523552B2 JP 5523552 B2 JP5523552 B2 JP 5523552B2 JP 2012506491 A JP2012506491 A JP 2012506491A JP 2012506491 A JP2012506491 A JP 2012506491A JP 5523552 B2 JP5523552 B2 JP 5523552B2
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- ritonavir
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Classifications
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Landscapes
- Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
何かの存在に付けられる「a」または「an」は、成句として、本明細書で用いられるように、その存在が1またはそれより多くであることを意味し、例えば、化合物(a compound)は、1種またはそれより多くの化合物、または、少なくとも1種の化合物を意味する。そのようなものとして、用語「1つの(a)」(または「an」)、「1またはそれより多くの」および「少なくとも1つの」は、本明細書において同義的に用いることができる。
本発明のさらにその他の実施態様において、HCVを治療するために、または、HCVを治療する医薬品を製造するために、α−、β−またはγ−インターフェロン、および/または、サイモシン、および/または、リバビリン、および/または、R7128を、R7227およびリトナビルと共に使用することが提供される。
本発明の実施態様において、式Iで示される化合物、リトナビル、および、任意に阻害剤使用に関する指示を含む説明書き(informational insert)を含む薬剤パックが提供される。
投与前の21日以内に、被検者をこの研究に参加できるかどうかに関してスクリーニングした。この研究に、14人の健康な志願者を登録した(n=14/グループ)。以下に投与スケジュールを説明する:
1日目、R7227投与の前にPKサンプル(5mL)を回収し(投与前)、さらに、R7227投与から0.5、1、1.5、2、2.5、3、3.5、4、6、8、12および24時間後に回収した。
Yij=μ+τi+sj+εij
式中、Yijは、分析されるPKパラメーターを意味し、μは、変換した可変値の全体の平均を意味し、τiは、治療の母数効果を意味し;sjは、被検者の変量効果を意味し;εijは(エラー)を意味する。ランダム偏差εijは、独立しており、ゼロ平均で正規分布しおり、共通の分散σ2を有すると考えられる。比較のためのτR7227+リトナビルのグループとτR7227のグループについて、ANOVAモデルから、比較グループに関して残差分散σ2および90%の信頼限界が推測された。対数変換した可変値(AUC0→∞およびCmax)に関して、真のグループ平均の比率、および、それに対応する未変換の可変値の平均の比率に関する最小二乗平均の差を累乗することと変換した値に関する信頼限界それぞれによって信頼限界を計算した。
Claims (13)
- 式Iで示される化合物およびリトナビルが、別々の投薬形態である、請求項1に記載の医薬。
- 前記別々の投薬形態が、ほぼ同時に投与される、請求項2に記載の医薬。
- 式Iで示される化合物およびリトナビルが、単一の投与形態で投与される、請求項1に記載の医薬。
- 請求項1で定義された式Iで示される化合物、その遊離塩基または医薬的に許容される塩と、チトクロームP450モノオキシゲナーゼ阻害剤またはその医薬的に許容される塩を含むC型肝炎ウイルス感染の治療薬であって、ここで該チトクロームP450モノオキシゲナーゼ阻害剤は、リトナビルまたはその医薬的に許容される塩である、上記治療薬。
- さらに、免疫調節剤、および/または、抗ウイルス剤、および/または、HCVのNS3/4Aプロテアーゼのその他の阻害剤、および/または、NS5Bポリメラーゼの阻害剤、および/または、広域ウイルス阻害剤、および/または、その他のチトクロームP−450阻害剤から選択される少なくとも1種の追加の物質を含む、請求項5に記載の治療薬。
- C型肝炎ウイルスNS3/4Aプロテアーゼ阻害剤R7227の生物学的利用率を増加させる医薬品を製造するための、R7227とチトクロームP450モノオキシゲナーゼ阻害剤との使用であって、ここで該チトクロームP450モノオキシゲナーゼ阻害剤の量は、チトクロームP450モノオキシゲナーゼ阻害剤の非存在下のR7227の血中濃度と比較して、R7227の血中濃度を高めるのに十分であり、ここで該チトクロームP450モノオキシゲナーゼ阻害剤は、リトナビルまたはその医薬的に許容される塩である、上記使用。
- 前記R7227およびリトナビルが、別々の投薬形態である、請求項7に記載の使用。
- 前記R7227およびリトナビルが、同時に投与される、請求項7に記載の使用。
- R7227およびリトナビル、ならびに少なくとも1種の追加の物質の使用であって、ここで該少なくとも1種の追加の物質は、免疫調節剤;抗ウイルス剤;HCVのNS3/4Aプロテアーゼのその他の阻害剤;NS5Bポリメラーゼの阻害剤;広域ウイルス阻害剤、および、その他のチトクロームP−450阻害剤から選択される、請求項7に記載の使用。
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---|---|---|---|---|
WO2010045266A1 (en) * | 2008-10-15 | 2010-04-22 | Intermune, Inc. | Therapeutic antiviral peptides |
AR075584A1 (es) | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
EP2455068A1 (en) * | 2010-11-09 | 2012-05-23 | F. Hoffmann-La Roche AG | Pharmaceutical composition for treating HCV infections |
GB2506085A (en) | 2011-10-21 | 2014-03-19 | Abbvie Inc | Combination treatment (eg with ABT-072 or ABT-333) of DAAS for use in treating HCV |
DE112012003510T5 (de) | 2011-10-21 | 2015-03-19 | Abbvie Inc. | Verfahren zur Behandlung von HCV umfassend mindestens zwei direkt wirkende antivirale Wirkstoffe, Ribavirin aber nicht Interferon |
US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
CN107964006A (zh) | 2012-01-11 | 2018-04-27 | 艾伯维公司 | 用于制备hcv蛋白酶抑制剂的方法 |
WO2014004674A2 (en) * | 2012-06-27 | 2014-01-03 | Abbvie Inc. | Methods for treating hcv |
MX2015004411A (es) | 2012-10-08 | 2016-04-06 | Abbvie Inc | Compuestos utiles para elaborar inhibidores de proteasa de virus de la hepatitis c (vhc). |
EP3620163A1 (en) * | 2014-05-01 | 2020-03-11 | Eiger Biopharmaceuticals, Inc. | Treatment of hepatitis delta virus infection |
US10076512B2 (en) | 2014-05-01 | 2018-09-18 | Eiger Biopharmaceuticals, Inc. | Treatment of hepatitis delta virus infection |
US11311519B2 (en) | 2014-05-01 | 2022-04-26 | Eiger Biopharmaceuticals, Inc. | Treatment of hepatitis delta virus infection |
CN107530338B (zh) | 2015-04-21 | 2020-12-01 | 艾格尔峰生物制药有限公司 | 包含洛那法尼和利托那韦的药物组合物 |
JP7129703B2 (ja) | 2016-04-28 | 2022-09-02 | エモリー ユニバーシティー | アルキン含有ヌクレオチド及びヌクレオシド治療組成物並びにそれらに関連した使用 |
CN117105928B (zh) * | 2023-08-22 | 2024-03-26 | 上海蓝木化工有限公司 | 一种蛋白酶抑制剂及其制备方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE143262T1 (de) | 1992-12-29 | 1996-10-15 | Abbott Lab | Inhibitoren der retroviralen protease |
IL110752A (en) | 1993-09-13 | 2000-07-26 | Abbott Lab | Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor |
US5559158A (en) | 1993-10-01 | 1996-09-24 | Abbott Laboratories | Pharmaceutical composition |
IL111991A (en) | 1994-01-28 | 2000-07-26 | Abbott Lab | Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent |
US6037157A (en) * | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
IL141438A0 (en) | 2000-02-23 | 2002-03-10 | Pfizer Prod Inc | Method of increasing the bioavailability and tissue penetration of azithromycin |
CN1446201A (zh) * | 2000-07-21 | 2003-10-01 | 先灵公司 | 用作丙型肝炎病毒ns3-丝氨酸蛋白酶抑制剂的新型肽 |
CN1726041A (zh) | 2002-12-16 | 2006-01-25 | 贝林格尔·英格海姆国际有限公司 | 含有非核苷反转录酶抑制剂(nnrti)以及细胞色素p450抑制剂如蛋白酶抑制剂的组合物的用途 |
CA2543696A1 (en) * | 2003-10-27 | 2005-05-12 | Vertex Pharmaceuticals Incorporated | Combinations for hcv treatment |
US20080161324A1 (en) * | 2006-09-14 | 2008-07-03 | Johansen Lisa M | Compositions and methods for treatment of viral diseases |
US20120220520A1 (en) * | 2006-10-17 | 2012-08-30 | Van T Klooster Gerben Albert Eleutherius | Bioavailable combinations for hcv treatment |
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