{{Short description|Two synergistic drugs chemically linked together to a single molecule}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{for|use polysubstance use of drugs that are not chemically linked together|Combination drug}} <!--SEE TALK REGARDING THIS REQUEST: {{missing information|things that blur the line with ordinary combination meds: co-salts such as dimenhydrinate linked via an ionic bond, co-crystals held together by H-bonds|date=December 2022}} --> A '''codrug''' consists of two drug moieties, generally "active against the same disease", that are joined through one or more covalent chemical bonds to create a single new chemical entity;<ref name=LauEtal2008/> they can also be described as a '''mutual prodrug''', recognising that a catabolic biosynthetic step is most often required to liberate the two drugs.<ref name = DasEtal2010/> While acting against the same disease, the two moities may operate via different mechanisms of action, and so display differing specific therapeutic effects.{{fact|date = July 2024}}<!--Moved this stray sentence from below, into lead.--> The recognised advantages of a codrug approach to small molecule drug design include the possibilities of (i) combined efficacies of the two drugs that are therapeutically synergistic, (ii) altered properties that improve the pharmacokinetics (e.g., halflife) of the codrug over its individually administered components (iii) improved modes of drug delivery, and (iv) masking of reactive functional groups of each component drug, possibly improving shelf life (as well as pharmacokinetics).<ref name=LauEtal2008>{{cite journal | vauthors = Lau WM, White AW, Gallagher SJ, Donaldson M, McNaughton G, Heard CM | title = Scope and limitations of the co-drug approach to topical drug delivery | journal = Current Pharmaceutical Design | volume = 14 | issue = 8 | pages = 794–802 | year = 2008 | pmid = 18393881 | doi = 10.2174/138161208784007653 }}</ref><ref name = DasEtal2010>{{cite journal | vauthors = Das N, Dhanawat M, Dash B, Nagarwal RC, Shrivastava SK | title = Codrug: an efficient approach for drug optimization | journal = European Journal of Pharmaceutical Sciences | volume = 41 | issue = 5 | pages = 571–588 | date = December 2010 | pmid = 20888411 | doi = 10.1016/j.ejps.2010.09.014 }}</ref>
==Elements of codrug design== {{unreferenced section|date = July 2024}} An effective codrug should be pharmacologically inactive in its own right but should release the constituent drugs upon biochemical breakage of the chemical linkage at the target tissue where their therapeutic effects are needed. As such, the chemical linkage (usually a covalent bond) should be subjectable to biodegradation, such as hydrolysis, by an enzymatic or non-enzymatic mechanism. The differential distribution of enzymes capable of catalyzing the breakage of the chemical linkage in different tissues may be exploited to achieve tissue-specific metabolism of the codrug to release the constituent drugs. <!-- == Motivation == {{unreferenced section|date=December 2022}} '''Development of Anticancer Codrugs [3]:''' The disadvantages associated with the co-delivery of physically combined chemotherapeutic drugs/agents often suffer from poor solubility, less membrane permeability, unimproved bioavailability, as well as poor selectivity for the targeted cells. Simply we can say that physically combine drugs always struggles with less improved pharmacokinetic properties. Where selectivity is a major issue in the complex environment of a targeted cell. Several codrugs reported in the literature for the anticancer drug delivery with improved pharmacokinetic properties may provide ideas to the pharmaceutical scientist for further drug development in various diseases. '''''Codrug of butyric acid and ATRA,''''' '''Codrug of ATRA and histone deacetylase inhibitors,''' '''''5-Fluorouracil (5-FU) and cytarabine (Ara-C) codrug,''''' '''''Paclitaxel and captopril codrug,''''' '''''5-Fluorouracil and diazeniumdiolate codrug,''''' --> ==Common codrugs== {{multiple issues|section = yes| {{expert needed|pharmacology|section|reason = to ascertain that all agents listed, especially those without a source, are indeed codrugs according to the definition supplied above|date = July 2024}} {{refimprove section|date = July 2024}} }} <!--Per WP:VERIFY, wikilinking cannot replace need for verifiable citations.--> * Sulfasalazine: Sulfapyridine linked via an azo group to 5-aminosalicylic acid. * Alpha-GPC: Choline linked to glycerophosphate. * Benorylate: Paracetamol linked via esterification to acetylsalicylic acid. * Cod-THC: THC linked via a carbonate group to codeine. * Fenethylline: Amphetamine linked to theophylline. * Sultamicillin: ampicillin linked via esterification to sulbactam. * Cefilavancin: a vancomycin derived antibiotic linked to a cephalosporin antibiotic. * Rifaquizinone: a rifamycin derived antibiotic linked to a quinolone antibiotic. * Proglumetacin: indometacin linked to proglumide * Dimenhydrinate: Diphenhydramine formed into a salt with 8-chlorotheophylline
== References == {{reflist}}
== See also == * Combination drug * Small molecule drug conjugate * Drug synergy * Ampicillin/sulbactam
Category:Codrugs
{{Combined substance use and adulteration}}