Drugs may work better at certain times of the day

“Take your medication at the right time of day or it might not work,” The Independent reports.

The news is based on a study which looked at the pattern of genes made in 12 different mouse organs, to see if any of the genes showed a circadian rhythm (the “body clock”: where the body reacts to a day and night cycle).

Nearly half of genes that code for proteins showed a circadian rhythm in at least one mouse organ.

In most organs, such as the liver, the researchers noted that the expression (activity) of many genes peaked during “rush hours” before dawn and dusk.

The researchers found that the majority of best-selling drugs, and medicines listed as “essential” by the World Health Organization (WHO), directly target products of rhythmic genes. As some of these drugs remain active for short periods (have short "half-lives"), the time the drug is taken could impact on how well it works.

However, in the wild, mice are primarily nocturnal (mainly active at night), in contrast to people who are diurnal (mainly active during the day), so the genes that are expressed in a circadian rhythm might be different.

Although this study suggests that medication timing could be modified to improve effectiveness, further studies will be required to determine optimal drug timing.

Where did the story come from?

The study was carried out by researchers from the University of Pennsylvania and the University of Missouri, and was funded by the US National Heart, Lung and Blood Institute, and by the Defense Advanced Research Planning Agency (DARPA).

The study was published in the peer-reviewed scientific journal PNAS. This article is open access, meaning that it can be read for free online.

This study was well covered by the UK media. BBC News also featured a useful infographic about the body clock and its impact on biological function.

What kind of research was this?

This was an animal study, which aimed to look at the pattern of the genes made in mice over a 24-hour period.

It should be noted that mice in the wild are primarily nocturnal, in contrast to people, who are diurnal, so the genes expressed in a circadian rhythm might be different. Although this study suggests medication timing could be modified to improve effectiveness, further studies will be required to determine optimal drug timing.

What did the research involve?

The researchers looked at the genes that were being made in 12 different mouse organs every two hours over a 48-hour period. The organs that they examined were the:

brainstem
cerebellum
hypothalamus
heart
aorta
kidney
adrenal gland
liver
lung
skeletal muscle
brown fat
white fat

They looked for genes that cycled over a 24-hour (one-day) period.

What were the basic results?

The researchers found that 43% of the genes that code for proteins show a circadian rhythm somewhere in the body.

The liver had the most circadian genes, whereas the hypothalamus (part of the brain) had the fewest.

In most organs, the researchers noted that the expression of many oscillating genes peaked during “rush hours”, before dawn and dusk.

The researchers also found that some genes that don’t code for proteins get expressed in a circadian rhythm.

The researchers found that the majority of best-selling drugs, and medicines listed as “essential” by the WHO, directly target products of rhythmic genes. As some of these drugs have short half-lives, the time the drug is taken could impact on how effective they are.

How did the researchers interpret the results?

This study found that nearly half of all genes in the mice oscillated with a circadian rhythm somewhere in the body. They go on to say that "a majority of best-selling drugs in the United States target circadian gene products. Many of these drugs have relatively short half-lives, and our data predict which may benefit from timed dosing.”

Conclusion

This study looked at the pattern of genes made in 12 different mouse organs, to see if any of the genes showed a circadian, or 24-hour, rhythm.

43% of the genes that code for proteins showed a circadian rhythm in at least one mouse organ. The liver had the most circadian genes, whereas the hypothalamus (part of the brain) had the fewest.

In most organs, the researchers noted that the expression of many oscillating genes peaked during “rush hours” before dawn and dusk.