Prodrugs

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Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination ADME features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting i. Keywords: ProTide; biopharmaceutics; drug absorption; drug delivery; drug targeting; oral administration; prodrugs.

Prodrugs

Federal government websites often end in. The site is secure. Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination ADME features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting i. Powerful modern drug discovery techniques, such as combinatorial chemistry and high-throughput screening, enable the discovery of novel chemical entities with high pharmacological efficacy [ 1 ]. These techniques have also created a new challenge, as many of the new drug candidates have unfavorable physicochemical features and still require chemical modification or use of formulation technologies to achieve adequate performance and pass the rigorous drug development process successfully [ 2 ]. Chemical modifications may range from creating salts for improved dissolution rate [ 3 ] to increasing lipophilicity, e. Various formulation technologies can be employed to overcome physicochemical obstacles [ 5 , 6 , 7 ], though they may or may not be successful in reaching adequate drug delivery. The prodrug approach represents a potentially effective solution to these obstacles [ 8 ]. Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into the active parent drug within the human body.

Population-based mechanistic prediction of oral drug absorption. Gene-directed prodrugs prodrug therapy. Sanghani, S.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two. Prodrugs have evolved from being serendipitously discovered or used as a salvage effort to being intentionally designed. Such efforts can avoid drug development challenges that limit formulation options or result in unacceptable biopharmaceutical or pharmacokinetic performance, or poor targeting.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The development of prodrugs is presently well established as a strategy for improving the physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically potent compounds and thereby overcoming barriers to a drug's developability and usefulness. Clinically, the majority of prodrugs are used with the aim of enhancing drug permeation by increasing drug lipophilicity and more recently to improve drug water solubility. This Review provides an overview of functional groups that are amenable to prodrug design, and highlights major applications of the prodrug strategy, including improving oral absorption, improving aqueous solubility, enhancing lipophilicity, enhancing active transport as well as achieving site-selective delivery.

Prodrugs

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two.

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Lam, A. Stappaerts, J. Besides, emerging computational methods play an important role in prodrug optimization and have the opportunity to significantly enhance the efficiency of the prodrug development process. Wikimedia Commons. Sun J. Bambuterol, a carbamate ester prodrug of terbutaline, as inhibitor of cholinesterases in human blood. Prodrugs can be developed for many routes of administration: oral, intravenous, intramuscular, inhalation, transdermal, and more [ 22 ]. Prediction of gastro-intestinal absorption using multivariate adaptive regression splines. Dictionary Entries Near prodrug. Pharmacokinetics and metabolism of selected prodrugs of PMEA in rats. Transport of L -valine-acyclovir via the oligopeptide transporter in the human intestinal cell line, Caco The discovery and process.

A prodrug is a pharmacologically inactive medication or compound that, after intake , is metabolized i. Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract.

Sorry, a shareable link is not currently available for this article. Nettles, R. Williams, E. This is the first prodrugs Review in Nature Reviews Drug Discovery that discusses various preclinical and clinical applications of prodrugs. Comparison of ampicillin and hetacillin pharmacokinetics in man. Amino acids as promoieties in prodrug design and development. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Leukemia 19 , — Drug Deliv. Intramuscular preparations of antipsychotics: uses and relevance in clinical practice. Srinivasarao, M.