Seasonal variation in blood drug concentrations and a potential relationship to vitamin D.

Drug Metab Dispos. 2011 May;39(5):933-7. Epub 2011 Feb 24.
Lindh JD, Andersson ML, Eliasson E, Björkhem-Bergman L.
Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital, Huddinge, SE 141 86 Stockholm, Sweden.

The most important enzyme in hepatic drug metabolism is cytochrome P450 3A4. Published in vitro data indicate that vitamin D may up-regulate the expression of the CYP3A4 gene. Individual vitamin D levels are highly dependent on sunlight exposure and show great seasonal variability in northern countries.

The aim of the present study was to investigate whether plasma concentrations of CYP3A4 drug substrates exhibit seasonal changes compatible with a stimulatory effect of vitamin D on drug metabolism. Three immunosuppressants (tacrolimus, sirolimus, and cyclosporine) were analyzed, because these CYP3A4 drug substrates are subject to long-term use and repeated concentration determinations. In addition, mycophenolic acid was included in the analysis as a control drug independent of CYP3A4 metabolism. Concentration-to-dose ratios were extracted from the Karolinska Therapeutic Drug Monitoring database and compared between the 3-month periods of lowest and highest vitamin D levels. Sirolimus and tacrolimus levels showed seasonal variability that was highly consistent with changes in vitamin D; for example, significantly lower drug concentrations in July to September than in January to March. As expected, no significant difference was evident for mycophenolic acid, but this result was also the case with cyclosporine, possibly due to cross-reactivity of CYP3A4-mediated metabolites with the immunoassay used for quantification.

In conclusion, there is cyclic variation in blood levels of important immunosuppressants throughout the year that correlates with UV light-dependent changes in vitamin D levels. Even though a causal relationship remains to be established, it is suggested that individual differences in vitamin D may contribute to variability in drug metabolism and disposition.

PMID: 21349923

FIG. 1.

A, monthly UV radiation in Stockholm, Sweden.
B, monthly serum levels of vitamin D (25OH vitamin D) in a Finnish cohort (n1136). Raw data was obtained from Virtanen et al. (2010).
C, monthly sirolimus C/D ratios in patients monitored at Karolinska (n344 patients).
D, monthly tacrolimus C/D ratios in patients monitored at Karolinska (n1671 patients).
All values are presented as deviations from the yearly average. Lines represent moving average of three adjacent months
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See also VitaminDWiki

• All items in Drug Interactions with Vitamin D 121 items
• Drugs which create a vitamin D deficiency
• Interactions of vitamin D with Drugs – 2010 NLM
• Vitamin D use with chemotherapy – July 2010

See also web

• Was reported by Dr. Soram Khalsa June 2011
  “This study, published in Drug Metabolism & Disposition, was the first of its kind to show that the body’s vitamin D level can affect the liver’s ability to break down and metabolize medication. This may give physicians and researchers insight into a puzzling question: Why do patients with otherwise similar medical histories respond differently to the same dosage of medicines?”
• The relationship between vitamin D and prescription drugs Vitamin D Council post on this study March 2011