Abstract
Treatment of health problems that accompany aging often includes pharmacotherapy. It is thus common for older adults—and, increasingly, younger adults—to be on multiple medications, either prescription or over-the-counter (OTC). With the consumption of multiple medications, drug-drug interactions (DDIs) are a concern. The site of drug-drug interactions is often at the level of drug metabolism. If a drug inhibits (or enhances) the metabolism of another, the blood level (therapeutic effect) can be decreased below the required level, or adverse effects can increase. Because most currently used drugs are metabolized via cytochrome P450-catalyzed pathways, drug discovers seek drugs that are metabolized by alternate pathways. Medicinal chemists have come upon a strategy—the incorporation of oxetane rings in the drug structure—that increases the likelihood that a drug will not be metabolized via CYP450. The same modification gives other desirable physical properties to the molecule. Although there are no guarantees that there will be fewer DDIs or an absence of other unexpected problems, the strategy could pave the way for new drugs that are safer and easier to use with concomitant medications.
Highlights
In the past century, populations in many parts of the world are aging [1]
Because most currently used drugs are metabolized via cytochrome P450-catalyzed pathways, drug discovers seek drugs that are metabolized by alternate pathways
Medicinal chemists have come upon a strategy—the incorporation of oxetane rings in the drug structure—that increases the likelihood that a drug will not be metabolized via CYP450
Summary
Populations in many parts of the world are aging [1]. And a significant rise in life expectancy in almost all regions of the world has contri-. Since the aging process predisposes a person to increased vulnerability and susceptibility to external threats and internal physiological decline in organ function and defensive processes against disease, concurrent with the increasing population is an increase in the needs for healthcare and related services [2] [3] (Figure 1). While not inherently a contraindication, polypharmacy can inadvertently lead to serious adverse consequences [11] [12] [13]. The occurrence of such an event is termed a “drug-drug interaction” (DDI). One of the major physiological mechanisms leading to a DDI is an interaction at the level of drug metabolism. A strategy that could limit the occurrence of a DDI at the level of CYP450 drug metabolism could have a significant benefit
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