The study will be published in the scientific journal Drug Metabolism & Disposition and is based on nearly 70,000 analyses from patients who have undergone regular monitoring of the levels of drugs in their blood. The drugs taken by these patients are used to suppress the immune system in association with organ transplants. Samples taken during the winter months were compared with those taken late in the summer.
A more detailed analysis showed that the concentrations of drugs such as tacrolimus and sirolimus, which are used to prevent rejection following transplantation, vary throughout the year in a manner that closely reflects changes in the level of vitamin D in the body. The ability of the body to form vitamin D depends on sunlight, and the highest levels in the patients taking part in the study were reached during that part of the year when the levels of the drugs were lowest.
The connection between sunlight, vitamin D and variations in drug concentration is believed to arise from the activation by vitamin D of the detoxification system of the liver by increasing the amount of an enzyme known as CYP3A4. This enzyme, in turn, is responsible for the breakdown of tacrolimus and sirolimus.
“If the breakdown capacity increases, then higher doses of a drug are normally required in order to achieve the same effect”, says Jonatan Lindh at the Department of Laboratory Medicine and one of the scientists who carried out the study. “More research will be needed to confirm the results, but CYP3A4 is considered to be the most important enzyme in drug turnover in the body, and the results may have significance for many drugs”
The effects of vitamin D on CYP3A4 have previously been demonstrated in experiments in cell cultures. But the study now to be published shows for the first time that the mechanism can play an important role in the pharmacological treatment of patients, and it shows for the first time that variation in exposure to sunlight may affect the sensitivity of individuals to drugs.
Karolinska Institutet is one of the world’s leading medical universities. It accounts for over 40 per cent of the medical academic research conducted in Sweden and offers the country’s broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine.
The publication: ‘Seasonal variation in blood drug concentrations and a potential relationship to vitamin D’, Lindh JD, Andersson ML, Eliasson E, Björkhem-Bergman L., Drug Metab Dispos, online ahead of print 24 February 2011, doi:10.1124/dmd.111.038125.
Caption: Jonatan Lindh, photo credit to Marianne Andersson.