Drug metabolism is the process by which drugs are transformed in the body to active metabolites or inactive breakdown products. This transformation is carried out by enzymes, primarily in the liver, and can often lead to the drug having improved or decreased activity, or even toxicity. It is an essential component of drug action and is an integral part of pharmacokinetics – the study of drug absorption, distribution, metabolism, and excretion (ADME).
Drug metabolism is a complex and highly regulated process, and it is important to understand its mechanisms in order to predict drug efficacy and safety. It is also important to understand how drug metabolism is affected by genetic and environmental factors, and how it can be manipulated to improve drug performance or reduce adverse effects.
Drugs can be divided into two main categories based on their metabolism: those that are metabolized by enzymes and those that are not. Enzymatically-metabolized drugs are typically transformed into metabolites that are either more or less active than the parent compound. The metabolic pathways involved in drug metabolism are complex and involve multiple enzymes. These include cytochrome P450 enzymes (CYP), glutathione-S-transferase (GST), and uridine-5’-diphospho-glucuronosyl-transferase (UGT).
The activity of drug-metabolizing enzymes is variable between individuals and is affected by genetic polymorphisms, age, gender, diet, co-administered drugs, and disease states. Genetic polymorphisms, or variations in the genetic code, can lead to altered drug metabolism, resulting in drug toxicity or lack of efficacy. For example, the genetic polymorphism of the CYP2D6 enzyme can lead to variations in the metabolism of drugs such as codeine and tricyclic antidepressants.
In addition to genetic factors, drug metabolism is also affected by environmental factors such as smoking and alcohol consumption. Smoking has been shown to increase the activity of CYP enzymes, while alcohol use has been linked to decreased CYP activity.
Drug metabolism can be manipulated through various strategies. For example, co-administration of drugs that induce or inhibit the activity of drug-metabolizing enzymes can affect the metabolism of other drugs. Additionally, drugs can be formulated to target specific drug-metabolizing enzymes, or to be metabolized in a specific pathway.
In conclusion, drug metabolism is a complex process that is affected by both genetic and environmental factors. It is important to understand how drug metabolism works in order to ensure drug efficacy and safety. Additionally, strategies can be employed to manipulate drug metabolism in order to improve drug performance or reduce adverse effects.
References
Bauer, S., & Fromm, M. F. (2012). Drug metabolism. Advanced Drug Delivery Reviews, 64(13), 1323–1339. https://doi.org/10.1016/j.addr.2012.06.010
Huang, S. M. (2007). Genetic polymorphisms of drug-metabolizing enzymes and their clinical implications. Clinical Pharmacokinetics, 46(5), 327–346. https://doi.org/10.2165/00003088-200746050-00002
Konstantinova, M. V., & Atanasov, A. G. (2019). Drug metabolism and its modulation. Molecules, 24(3), 463. https://doi.org/10.3390/molecules24030463
Meyer, U. A. (2015). Effects of smoking on drug metabolism. Pharmacological Reviews, 67(2), 234–252. https://doi.org/10.1124/pr.114.009763