No major effects of vitamin D(3) (1,25 dihydroxyvitamin D(3)) on absorption and pharmacokinetics of folic acid and fexofenadine in healthy volunteers

PURPOSE: In Caco-2 cells, folate uptake via the proton-coupled folate transporter (PCFT) increases significantly by a 3-day treatment with 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Additionally, mRNA content and protein expression of the transporter OATP1A2 were increased up to ninefold with 1,25(OH)(2)D(3). We investigated whether these in vitro findings can be confirmed in humans in vivo. METHODS: Ten healthy volunteers (six women) received 5 mg folic acid orally once before and once together with the last intake of a 10-day course of 0.5 μg 1,25(OH)(2)D(3) orally. One hundred twenty milligrams fexofenadine, an OATP1A2 substrate, was taken in 1 day before the first folic acid intake, and again on the ninth day of 1,25(OH)(2)D(3) intake. Duodenal biopsies were taken for transporter mRNA assessments once before and once on the ninth or tenth day of the vitamin D(3) course. Serum folic acid and fexofenadine concentrations were quantified with a chemiluminescence immunoassay and LC-MS/MS, respectively. Pharmacokinetics were compared between periods with standard bioequivalence approaches. RESULTS: While geometric mean folic acid AUC(0-2h), which mainly reflects absorption, was 0.403 and 0.414 mg/L·h before and after the vitamin D(3) course (geometric mean ratio (GMR), 1.027; 90 % confidence interval (90 % CI), 0.788–1.340), the geometric mean fexofenadine AUC(0-2h) was 1.932 and 2.761 mg/L·h, respectively (GMR, 1.429; 90 % CI, 0.890–2.294). PCFT- and OATP1A2-mRNA expressions in duodenal biopsies were essentially unchanged. CONCLUSIONS: No significant changes in folic acid and fexofenadine absorption were observed after a 10-day course of 1,25(OH)(2)D(3) in humans in vivo. This study underlines the importance of confirming in vitro findings in vivo in humans.