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Time of day or night drug taken 'impacts on effectiveness'

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A body-clock “atlas” mapping the 24-hour activity patterns of thousands of genes has been created by US scientists.

The five-year-long project is expected to provide important clues about the way drug effects may be influenced by timing – for instance, taking a medicine in the morning or at night.

“Now we know which drug targets are under clock control and where and when they cycle in the body”

John Hogenesch

The research showed that most best-selling medicinal drugs target proteins made by genes whose activity changes daily.

Timing is an important but often ignored factor in drug effectiveness, the scientists point out in the journal Proceedings of the National Academy of Sciences.

Dr Michael Hughes, a member of the team from the University of Missouri-St Louis, said: “The genome is under much more clock control than we once thought.

Timing 'impacts drug effectiveness'

“Since only a few organs were studied previously, we were only looking under the lamp-post. Now we have the most comprehensive survey to date.”

The research, conducted on mice, showed that 43% of all protein-coding genes were subject to “circadian rhythms”, or 24-hour body clock cycles.

The liver was the most rhythmic of the 12 organs studied, having more clock-like genes than any other.

Many clock genes peaked in activity during the “rush hours” of transcription – the process by which the genetic code is transcribed to allow protein production – preceding dawn and dusk.

Of 100 top-selling drugs, 56 targeted genes with circadian patterns of activity. This was also true of 119 of the World Health Organization’s list of 250 “essential” medicines.

University of Pennsylvania

John Hogenesch

“Most of these drug targets were not known to be clock-regulated,” said co-author Professor John Hogenesch, from the University of Pennsylvania.

“Many metabolising enzymes and transporters are too. Because this isn’t appreciated, few of these drugs have been evaluated for time-of-day dependent efficacy, metabolism, or toxicity.

“Now we know which drug targets are under clock control and where and when they cycle in the body. This provides an opportunity for prospective chronotherapy.”

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