Metabolism and pharmacokinetics of vitamin D in patients with cystic fibrosis

Abstract

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)D₂ and 25(OH)D₃, 1α,25-dihydroxyvitamins D₂ and D₃ (1α,25(OH)₂D₂ and 1α,25(OH)₂D₃), 24,25-dihydroxyvitamin D₃ (24,25(OH)₂D₃), 4β,25-dihydroxyvitamin D₃ (4β,25(OH)₂D₃), 25-hydroxyvitamin D₃-3-sulfate (25(OH)D₃-S), and 25-hydroxyvitamin D₃-3-glucuronide (25(OH)D₃-G). In a 56-day prospective pharmacokinetic study, ∼25 μg deuterium-labeled 25(OH)D₃ (d₆-25(OH)D₃) was administered intravenously to participants (N = 5 with CF, N = 5 control subjects). Serum was analyzed for d₆-25(OH)D₃ and d₆-24,25(OH)₂D₃, 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)₂D (43.6 [12.7] vs. 50.7 [13.0] pg/mL), 4β,25(OH)₂D₃ (52.1 [38.9] vs. 79.9 [60.2] pg/mL), and 25(OH)D₃-S (17.7 [11.6] vs. 30.1 [12.3] ng/mL) (p < 0.001 for all). The pharmacokinetics of d₆-25(OH)D₃ and d₆-24,25(OH)D₃ did not differ between groups. In summary, although 25(OH)D concentrations were comparable, participants with CF had lower 1α,25(OH)₂D, 4β,25(OH)₂D₃, and 25(OH)D₃-S concentrations than healthy controls. Neither 25(OH)D₃ clearance, nor formation of 24,25(OH)₂D₃, 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.

Keywords: 1α,25-dihydroxyvitamin D; 24,25-dihydroxyvitamin D; 25-hydroxyvitamin D; Cystic fibrosis; Pharmacokinetics.