ヒトの腸内細菌による治療薬の生物蓄積
Martina Klünemann1,2, Sergej Andrejev1,3, Sonja Blasche1,4
1European Molecular Biology Laboratory, Heidelberg, Germany.
Nature
|September 9, 2021
まとめ
腸内細菌は 薬の蓄積という過程で 薬の効能と代謝に影響を及ぼします この相互作用は,薬剤の可用性,微生物群の組成,および個々の薬剤反応に影響します.
科学分野:
- 微生物学
- 薬理学について
- 薬物の代謝
背景:
- 腸内細菌は薬の利用可能性と有効性に影響します
- バイオトランスフォーメーションは,薬と微生物の相互作用の主要な提案されたメカニズムです.
- 薬物とバクテリアの相互作用を 体系的にマッピングすることは 最近の発展です
研究 の 目的:
- 腸内細菌による薬物の消耗を調査する
- 新しい細菌と薬の相互作用を 特定するためです
- 薬物の生物蓄積のメカニズムを解明する.
主な方法:
- 15種類の薬剤を 25種類のバクテリア菌株に対して 検診しています
- クリック化学,熱プロテオームプロファイリング,メタボロミックスを用いてドロキセチンの生物蓄積を調査する.
- 定義された微生物コミュニティとCaenorhabditis elegansの動物モデルでの試験効果
主要な成果:
- バクテリアと薬物の相互作用が 70 件見つかりました
- 新しい相互作用の半分以上は生物蓄積 (細胞内薬物貯蔵) に起因する.
- デュロキセチンの生物蓄積は,細菌の代謝,コミュニティの構成,宿主反応を変化させる.
結論:
- 生物蓄積は,薬剤の利用可能性と細菌の代謝を変化させる一般的なメカニズムです.
- これは微生物群の組成,薬動力学,個々の薬剤反応に影響します.
- パーソナライズド医療と薬物開発に 影響を及ぼします
関連する概念動画
Drug Distribution: Tissue Binding
3.5K
Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
For...
3.5K
Drug Biotransformation: Overview
3.1K
Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
3.1K
Hepatic Drug Excretion: Enterohepatic Cycling
1.9K
Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
1.9K
Factors Influencing Drug Absorption: Disease States and Pharmacology
974
Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
974
Factors Influencing Bioavailability: First-Pass Elimination
7.3K
When a drug is taken orally, it undergoes a journey starting from the gastrointestinal (GI) tract, passing through the portal vein, reaching the liver, and finally entering the systemic circulation. This process involves the absorption of the drug across the GI tract. The liver is the primary site for metabolizing the drug, with some metabolism also occurring in the gut wall. This journey significantly reduces the quantity of the drug that reaches the systemic circulation, a phenomenon known as...
7.3K
Drug Absorption: Factors Affecting GI Absorption
5.2K
The process of oral drug absorption can be influenced by several factors. Weakly acidic drugs tend to be absorbed more readily from the stomach due to their nonionized state. However, absorption may be less efficient in the upper intestine, where drugs are often ionized. Interestingly, despite the stomach's apparent advantage for drug absorption, its mucous layer can hinder diffusion. Its surface area is also smaller than the intestine's, which can further slow down the absorption rate.
5.2K


