Codrug


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; they can also be described as a mutual prodrug, recognising that a catabolic biosynthetic step is most often required to liberate the two drugs. While acting against the same disease, the two moities may operate via different mechanisms of action, and so display differing specific therapeutic effects. The recognised advantages of a codrug approach to small molecule drug design include the possibilities of combined efficacies of the two drugs that are therapeutically synergistic, altered properties that improve the pharmacokinetics of the codrug over its individually administered components improved modes of drug delivery, and masking of reactive functional groups of each component drug, possibly improving shelf life.

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 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