Codrug

A codrug or mutual prodrug consists of two synergistic drugs chemically linked together, in order to improve the drug delivery properties of one or both drugs. The constituent drugs are indicated for the same disease, but may exert different therapeutic effects via disparate mechanisms of action.

Some examples of codrugs include:

• Sulfasalazine, which is a combination of sulfapyridine and 5-aminosalicylic acid coupled with an azo linkage
• Benorylate, which is an esterified product of paracetamol and acetylsalicylic acid
• Sultamicillin, which is an ester of ampicillin and sulbactam

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.