Swedish researchers uncover link between sunlight and drug kinetics

The team from the Karolinska Institute in Stockholm, Sweden said their findings point to the idea that drug efficacy varies with the seasons and may offer a completely new model to explain how drugs affect different individuals.

The study, to be published in the scientific journal 'Drug Metabolism & Disposition' was based on nearly 70,000 analyses from patients taking the immunosuppressant drugs tacrolimus and sirolimus after organ transplants. Samples were taken in late summer and compared with those taken in winter.

They found that the concentration of drugs in a patient's body varied throughout the year “in a manner that closely reflects changes of vitamin D.”​

Breakdown capacity​

The body forms vitamin D when exposed to sunlight, and the highest levels in patients taking part in the study were reached during that part of the year when the levels of drugs were lowest.

The connection between sunlight, vitamin D and variations in drug concentration is based on the activation by vitamin D of the liver's detoxification system and the subsequent release of an enzyme known as CYP3A4.

“If the breakdown capacity increases, then higher doses of a drug are normally required in order to achieve the same effect,” ​said Jonatan Lindh one of the researchers at the Institute's department of laboratory medicine, “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.”​

Pairwise comparisons​

Speaking to in-PharmaTechnologist, Erik Eliasson, a member of the research team and an associate professor at the Institute, explained: “We focused on classical immunosuppressants since they are measured many times over long periods even in a single patient. That allowed us to make pairwise comparison between dark and bright periods of the year.​

“But even unpaired analysis with more observations were statistically different between the periods. And we could actually use many more results sampled all over the year to find the cyclic change over the seasons.​

“The idea was quite simple, but we had the tools to test it.”​

Therapeutic index​

Eliasson suggested the findings may be of benefit to doctors working in a number of fields to help them better tailor treatments based on an individual's needs.

“I think drugs with a fairly narrow therapeutic index that are not subject to routine monitoring by concentration determinations may benefit from this additional explanation” ​he said. “Perhaps it will help for instance doctors in psychiatry or cardiology to understand the actual exposure level and presumably therefore the therapeutic effect may vary over the year.”​

However, Eliasson stopped short of suggesting the team's findings pave the way for bespoke dosage levels linked to the time of year.

“Too early to say,” ​he said, “but we need better predictors of the capacity to eliminate drugs in individual patients. To some extent we may circumvent this uncertainty by measuring the drug levels. But perhaps the vitamin D level in a patient may be of some predictive value.”​