METABOLISM AND PHARMACOKINETICS OF VITAMIN D in PATIENTS with Cystic Fibrosis.

Patients with cystic fibrosis (CF) commonly have lower circulating concentrations of 25-hydroxyvitamin D (25(OH)D) than healthy populations. We comprehensively compared measures of vitamin D metabolism among individuals with CF and healthy control subjects. In a cross-sectional study, serum from participants with CF (N=83) and frequency-matched healthy control subjects by age and race (N=82) were analyzed for: 25(OH)D and 25(OH)D, 1α,25-dihydroxyvitamins D and D (1α,25(OH)D and 1α,25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)D), 4β,25-dihydroxyvitamin D (4β,25(OH)D), 25-hydroxyvitamin D-3-sulfate (25(OH)D-S), and 25-hydroxyvitamin D-3-glucuronide (25(OH)D-G). In a 56-day prospective pharmacokinetic study, ~25μg deuterium-labeled 25(OH)D (d-25(OH)D) was administered intravenously to participants (N=5 with CF, N=5 control subjects). Serum was analyzed for d-25(OH)D and d-24,25(OH)D, and pharmacokinetic parameters were estimated. In the cross-sectional study, participants with CF had similar mean (SD) total 25(OH)D concentrations as control subjects (26.7 [12.3] vs. 27.7 [9.9] ng/mL) and had higher vitamin D supplement use (53% vs. 22%). However, participants with CF had lower total 1α,25(OH)D (43.6 [12.7] vs. 50.7 [13.0] pg/mL), 4β,25(OH)D (52.1 [38.9] vs. 79.9 [60.2] pg/mL), and 25(OH)D-S (17.7 [11.6] vs. 30.1 [12.3] ng/mL) (p < 0.001 for all). The pharmacokinetics of d-25(OH)D and d-24,25(OH)D did not differ between groups. In summary, although 25(OH)D concentrations were comparable, participants with CF had lower 1α,25(OH)D, 4β,25(OH)D, and 25(OH)D-S concentrations than healthy controls. Neither 25(OH)D clearance, nor formation of 24,25(OH)D, appears to account for these differences and alternative mechanisms for low 25(OH)D in CF (i.e., decreased formation, altered enterohepatic recirculation) should be explored.