Codrug

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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; [1] they can also be described as a mutual prodrug , recognising that a catabolic biosynthetic step is most often required to liberate the two drugs. [2] While acting against the same disease, the two moities may operate via different mechanisms of action, and so display differing specific therapeutic effects.[ citation needed ] 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 indivially 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). [1] [2]

Contents

Elements of codrug design

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.

Common codrugs

Related Research Articles

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<span class="mw-page-title-main">Tetrahydrocannabinol</span> Chemical compound

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<span class="mw-page-title-main">Glycoprotein</span> Protein with oligosaccharide modifications

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<span class="mw-page-title-main">Cannabinol</span> Naturally-occurring cannabinoid

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<span class="mw-page-title-main">Sultamicillin</span> Chemical compound

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<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

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<span class="mw-page-title-main">PEGylation</span> Chemical reaction

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<span class="mw-page-title-main">Retrometabolic drug design</span>

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References

  1. 1 2 Lau, W.M.; White, A.W.; Gallagher, S. J.; Donaldson, M.; McNaughton, G. & Heard, C.M. (2008). "Scope and Limitations of the Co-Drug Approach to Topical Drug Delivery". Current Pharmaceutical Design. 14 (8): 794–802. doi:10.2174/138161208784007653. PMID   18393881.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. 1 2 Das, N.; Dhanawat, M.; Dash, B.; Nagarwal, R.C. & Shrivastava, S.K. (2010). "Codrug: An Efficient Approach for Drug Optimization". European Journal of Pharmaceutical Sciences. 41 (5): 571–588. doi:10.1016/j.ejps.2010.09.014. PMID   20888411.{{cite journal}}: CS1 maint: multiple names: authors list (link)

See also