Abstract
The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolising CYP3A enzymes. In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated. Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomised to either placebo or high dose (4000 IU/day) vitamin D for 12 months. 116 patients were included in the final analyses and serum samples collected 6 months after study start were analysed. At this time point, 25-hydroxyvitamin D levels were found to range between 10-284 nmol/ L. Individual levels of 25-hydroxyvitamin D as well as CRP were compared with 4β-hydroxycholesterol levels. In addition, all participants were genotyped for two polymorphisms (Taq1 and Foq1) in the vitamin D receptor gene (VDR). There was no significant correlation between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol. However, a moderate, but statistically significant, negative correlation between CRP and 4β-hydroxycholesterol levels was observed. This study in patients with highly variable serum levels of 25-hydroxyvitamin D could not reveal any relationship between vitamin D and 4β-hydroxycholesterol, an endogenous biomarker of CYP3A activity. However, the negative correlation between CRP and 4β-hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration.
- CYP expression
- CYP gene regulation
- CYP induction
- CYP inhibition
- CYP3A
- drug interactions
- extrahepatic cytochrome P450
- pharmacokinetics
- vitamin D
- Received January 15, 2013.
- Accepted February 5, 2013.
- The American Society for Pharmacology and Experimental Therapeutics