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

作者：Kullak Ublick Gerd A; Gubler Christoph; Spanaus Katharina; Ismair Manfred G; da Silva Tatiana Claro; Jetter Alexander^*

来源：European Journal of Clinical Pharmacology, 2016, 72(7): 797-805.

DOI：10.1007/s00228-016-2050-0

• Absorption
• 1,25-dihydroxyvitamin D-3
• Fexofenadine
• Folic acid
• PCFT
• OATP1A2

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.
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 mu g 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.
While geometric mean folic acid AUC(0-2h), which mainly reflects absorption, was 0.403 and 0.414 mg/L center dot 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 center dot h, respectively (GMR, 1.429; 90 % CI, 0.890-2.294). PCFT- and OATP1A2-mRNA expressions in duodenal biopsies were essentially unchanged.
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.

• 出版日期2016-7