TY - JOUR T1 - Serum Levels of 25-Hydroxyvitamin D and the CYP3A Biomarker 4<em>β</em>-Hydroxycholesterol in a High-Dose Vitamin D Supplementation Study JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 704 LP - 708 DO - 10.1124/dmd.113.051136 VL - 41 IS - 4 AU - Linda Björkhem-Bergman AU - Hanna Nylén AU - Anna-Carin Norlin AU - Jonatan D. Lindh AU - Lena Ekström AU - Erik Eliasson AU - Peter Bergman AU - Ulf Diczfalusy Y1 - 2013/04/01 UR - http://dmd.aspetjournals.org/content/41/4/704.abstract N2 - 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-metabolizing 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 randomized to either placebo or high-dose (4000 IU/day) vitamin D for 12 months. One hundred sixteen patients were included in the final analyses, and serum samples collected 6 months after study start were analyzed. At this time point, 25-hydroxyvitamin D levels were found to range between 10 and 284 nM. 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. 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. ER -