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  • Nick Walker

Chronotherapeutics


Across diseases, from cancer and cardiac ailments to allergies and arthritis, research and clinical trials are revealing that timing medications to the body’s internal clock could improve their effectiveness and reduce side effects.


As I’m currently working with a company developing therapeutics to control circadian rhythms this feels like the other side of the coin which I thought was worth looking into.


As early as the 1970’s research data was emerging that showed that the timing of exposure to toxins, x-rays or drugs could alter the effects of these agents. For example, research into cholesterol regulation in humans showed that short-acting drugs such as simvastatin, which is still prescribed today, are most effective when taken at bedtime.


Genes involved in cell division were among the earliest identified as being rhythmically expressed in both rodent models and human cells. In 1987, researchers studying ovarian cancers found that tumour cells synthesized DNA on a daily rhythm that typically peaked in the late morning hours, nearly 12 hours out of sync with non-tumour cells. This led the team to suggest that timing chemotherapy doses that target cells actively replicating their DNA might improve the drugs’ effectiveness while reducing healthy-cell death.


Sure enough, over the past 30 years, experimental models and clinical trials have found that timing chemo treatments can significantly affect their toxicity and effectiveness. In animal studies of nearly 30 chemo drugs, tailoring dosing time to the medication’s mode of action has been found to decrease toxic side effects and increase effectiveness.


Even as chronotherapy was gaining recognition in the oncology research community, investigators realised that cancer was not the only disease likely to be affected by circadian cycles. Clinical trials in 1985 found that antihistamines were most effective when taken at night or early in the morning. Subsequent studies established that inhaling corticosteroids at bedtime or using delayed-release formulations that allocated the medication to the body pre-dawn, were most effective at combatting allergy symptoms. Cardiovascular events were also recognised early on to cycle throughout the day, as doctors noticed that most patients admitted for heart attacks tended to experience their symptoms between 6:00 a.m. and noon.


Similarly there are quite a few established time-related effects on the body;


  • alertness is at a maximum at 10:00 am (boosted by the stress hormone cortisol) and short-term memory optimal in the morning.

  • the best time for heart surgery is in the afternoon where subjects are half as likely to suffer a major cardiac event in the next 500 days when compared to their morning counterparts.

  • digestion of food results in a drop of alertness in the early afternoon and there is a noticeable rise in road deaths from 14:00.

  • the best lung and cardiovascular performance is at around 17:00, the heart and lungs work better and muscles are 6% stronger than at their lowest point in the day.

  • the highest blood pressure is around 18:30 and the highest body temperature at 19:00.

  • fastest reaction times are around 15:30.

  • overnight is a bad time to heal – a recent study shows that night time burns took an average of 11 days longer to heal than those incurred during the day.

So, timing medication to be “in tune” with the circadian rhythm of the patient has been shown to have significant importance, but there’s still quite a bit about the effect of circadian rhythms on the body that we don’t understand.


One thing we can be sure of is that chronotherapeutics is likely to have more significance in the future.


www.labrador.technology

email: nick@labrador.technology              tel: 07825 709418