Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA.
Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA.
J Steroid Biochem Mol Biol. 2023 Sep;232:106332. doi: 10.1016/j.jsbmb.2023.106332. Epub 2023 May 20.
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, ∼25 μg 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.
囊性纤维化 (CF) 患者的循环 25-羟维生素 D（25(OH)D）浓度通常低于健康人群。我们综合比较了 CF 患者和健康对照个体的维生素 D 代谢指标。在一项横断面研究中，分析了 83 名 CF 患者（N=83）和年龄和种族匹配的健康对照个体（N=82）的血清样本：25(OH)D 和 25(OH)D、1α,25-二羟维生素 D 和 D（1α,25(OH)D 和 1α,25(OH)D)、24,25-二羟维生素 D（24,25(OH)D）、4β,25-二羟维生素 D（4β,25(OH)D）、25-羟维生素 D-3-硫酸盐（25(OH)D-S）和 25-羟维生素 D-3-葡糖苷酸（25(OH)D-G）。在一项为期 56 天的前瞻性药代动力学研究中，静脉注射约 25μg 氘标记 25-羟维生素 D（d-25(OH)D）至参与者（CF 患者 5 名，对照组 5 名）。分析血清中的 d-25(OH)D 和 d-24,25(OH)D，并估计药代动力学参数。在横断面研究中，CF 患者的总 25(OH)D 浓度与对照组相似（26.7[12.3] vs. 27.7[9.9]ng/mL），并且维生素 D 补充剂使用率更高（53% vs. 22%）。然而，CF 患者的总 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）和 25(OH)D-S（17.7[11.6] vs. 30.1[12.3]ng/mL）（所有 p 值均<0.001）均较低。d-25(OH)D 和 d-24,25(OH)D 的药代动力学无差异。总之，尽管 25(OH)D 浓度相似，但 CF 患者的 1α,25(OH)D、4β,25(OH)D 和 25(OH)D-S 浓度低于健康对照组。25(OH)D 清除率或 24,25(OH)D 的形成似乎都不能解释这些差异，CF 中 25(OH)D 水平降低的其他机制（即形成减少、肠肝再循环改变）应加以探讨。
