Codrug
Encyclopedia
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:
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.
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
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 sulfapyridineSulfapyridineSulfapyridine, original UK spelling Sulphapyridine, is a sulfonamide antibacterial. At one time it was commonly referred to as M&B....
and 5-aminosalicylic acid coupled with an azo linkage - Benorylate, which is an esterified product of paracetamolParacetamolParacetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
and acetylsalicylic acid - SultamicillinSultamicillinSultamicillin is an oral form of the antibiotic combination ampicillin/sulbactam. It contains esterified ampicillin and sulbactam and is marketed under a number of trade names, including Saltum and Unasyn- References :...
, which is an ester of ampicillinAmpicillinAmpicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
and sulbactamSulbactamSulbactam is a molecule that is given in combination with beta-lactam antibiotics to inhibit beta-lactamase, an enzyme produced by bacteria that destroys the antibiotics...
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
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
) 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.