Codrug
A codrug or "mutual prodrug" consists of two synergistic drugs chemically linked together to a single molecule, in order to improve the drug delivery properties of one or both drugs.[1][2]
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.
The constituent drugs are indicated for the same disease, but may exert different therapeutic effects via disparate mechanisms of action.
Examples
Some examples of codrugs:
- Benorylate, which is an esterified product of paracetamol and acetylsalicylic acid
- Fenethylline, which is a combination of amphetamine and theophylline
- Lisdexamfetamine, which is a combination of dextroamphetamine and Lysine, enzymatic cleavage Lisdexamfetamine occurs at a consistent rate, releasing the dexamphetamine into the bloodstream along with mostly inert l-lysine, an amino acid with minimal biological effects in this case, to maintain steady concentration for 12-16 hours; often used for a full day of ADHD treatment, using a once daily dosing schedule. [3]
- Sulfasalazine, which is a combination of sulfapyridine and 5-aminosalicylic acid coupled with an azo linkage. It is on the World Health Organization's List of Essential Medicines.
- Sultamicillin, which is esterified ampicillin/sulbactam.
References
- W. M. Lau (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.
- N. Das (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.
- "Lisdexamfetamine Dimesylate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 April 2019.