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Charles W. Bishop - One of the best experts on this subject based on the ideXlab platform.
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Extended-Release Calcifediol in Renal Disease
Vitamin D, 2018Co-Authors: Martin Petkovich, Charles W. BishopAbstract:Abstract Vitamin D supplementation in chronic kidney disease (CKD) is recommended by current clinical practice guidelines, but is unreliable in correcting vitamin D insufficiency and ineffective for treating secondary hyperparathyroidism (SHPT). Vitamin D receptor agonist therapy can lower elevated parathyroid hormone, but leaves serum total 25-hydroxyvitamin D (25(OH)D) uncorrected, depriving tissues of adequate substrate for local 1,25-dihydroxyvitamin D (1,25(OH)2D) production. Such therapy also causes unwanted elevation of Fibroblast Growth Factor 23 and CYP24A1-mediated vitamin D catabolism, both of which are associated with resistance to vitamin D therapy, and increases calcium and phosphorus “burden.” This drives vascular and renal calcification, leading to morbidity, mortality, and increased costs of associated medical care. Recently, an extended-release Calcifediol formulation has been demonstrated in randomized controlled clinical trials to be a safe and effective treatment for SHPT associated with vitamin D insufficiency in patients with stage 3 or 4 CKD, overcoming challenges associated with prior and current therapies.
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extended release Calcifediol for secondary hyperparathyroidism in stage 3 4 chronic kidney disease
Expert Review of Endocrinology & Metabolism, 2017Co-Authors: Stuart M. Sprague, Stephen A. Strugnell, Charles W. BishopAbstract:ABSTRACTIntroduction: Extended-release Calcifediol (ERC) 30 µg capsules were recently approved as Rayaldee® by the United States Food and Drug Administration (FDA) for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3–4 (not 5) chronic kidney disease (CKD) and vitamin D insufficiency (serum total 25-hydroxyvitamin D < 30 ng/mL). Calcifediol is 25-hydroxyvitamin D3, a prohormone of calcitriol (1,25-dihydroxyvitamin D3), the endogenous active vitamin D hormone. ERC capsules have a lipophilic fill which gradually releases Calcifediol, corrects vitamin D insufficiency and increases serum calcitriol and thereby suppresses production of parathyroid hormone (PTH) in CKD patients without perturbing normal vitamin D and mineral metabolism.Areas covered: This review focuses on the chemical, pharmacokinetic, pharmacodynamic and clinical profiles of ERC and describes the product’s utility relative to other current treatment options for SHPT.Expert commentary: Randomized clinical trials (RCT...
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Extended-release Calcifediol for secondary hyperparathyroidism in stage 3-4 chronic kidney disease
Expert review of endocrinology & metabolism, 2017Co-Authors: Stuart M. Sprague, Stephen A. Strugnell, Charles W. BishopAbstract:ABSTRACTIntroduction: Extended-release Calcifediol (ERC) 30 µg capsules were recently approved as Rayaldee® by the United States Food and Drug Administration (FDA) for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3–4 (not 5) chronic kidney disease (CKD) and vitamin D insufficiency (serum total 25-hydroxyvitamin D
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Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.
American journal of nephrology, 2016Co-Authors: Stuart M. Sprague, Paul W Crawford, Joel Z. Melnick, Stephen A. Strugnell, Shaukat Ali, Roberto Mangoo-karim, Sungchun Lee, P. Martin Petkovich, Charles W. BishopAbstract:Background/Aims: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) Calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Methods: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER Calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER Calcifediol was administered without interruption for another 26 weeks. Results: ER Calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER Calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER Calcifediol was independent of CKD stage and significantly greater than with placebo. ER Calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Conclusion: Oral ER Calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.
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Modified-release oral Calcifediol corrects vitamin D insufficiency with minimal CYP24A1 upregulation
The Journal of steroid biochemistry and molecular biology, 2014Co-Authors: Martin Petkovich, Joel Z. Melnick, Jay A. White, Samir P. Tabash, Stephen Strugnell, Charles W. BishopAbstract:Vitamin D insufficiency is prevalent in chronic kidney disease (CKD) and associated with secondary hyperparathyroidism (SHPT) and increased risk of bone and vascular disease. Unfortunately, supplementation of stage 3 or 4 CKD patients with currently recommended vitamin D2 or D3 regimens does not reliably restore serum total 25-hydroxyvitamin D to adequacy (≥30ng/mL) or effectively control SHPT. Preclinical and clinical studies were conducted to evaluate whether the effectiveness of vitamin D repletion depends, at least in part, on the rate of repletion. A modified-release (MR) oral formulation of Calcifediol (25-hydroxyvitamin D3) was developed which raised serum 25-hydroxyvitamin D3 and calcitriol levels gradually. Single doses of either bolus intravenous (IV) or oral MR Calcifediol were administered to vitamin D deficient rats. Bolus IV Calcifediol produced rapid increases in serum 25-hydroxyvitamin D3, calcitriol and FGF23, along with significant induction of CYP24A1 in both kidney and parathyroid gland. In contrast, oral MR Calcifediol produced gradual increases in serum 25-hydroxyvitamin D3 and calcitriol and achieved similar hormonal exposure, yet neither CYP24A1 nor FGF23 were induced. A 10-fold greater exposure to bolus IV than oral MR Calcifediol was required to similarly lower intact parathyroid hormone (iPTH). Single doses of oral MR (450 or 900μg) or bolus IV (450μg) Calcifediol were administered to patients with stage 3 or 4 CKD, SHPT and vitamin D insufficiency. Changes in serum 25-hydroxyvitamin D3 and calcitriol and in plasma iPTH were determined at multiple time-points over the following 42 days. IV Calcifediol produced abrupt and pronounced increases in serum 25-hydroxyvitamin D3 and calcitriol, but little change in plasma iPTH. As in animals, these surges triggered increased vitamin D catabolism, as evidenced by elevated production of 24,25-dihydroxyvitamin D3. In contrast, MR Calcifediol raised serum 25-hydroxyvitamin D3 and calcitriol gradually, and meaningfully lowered plasma iPTH levels. Taken together, these studies indicate that rapid increases in 25-hydroxyvitamin D3 trigger CYP24A1 and FGF23 induction, limiting effective exposure to calcitriol and iPTH reduction in SHPT. They also support further investigation of gradual vitamin D repletion for improved clinical effectiveness. This article is part of a Special Issue entitled "17th Vitamin D Workshop".
G. Iolascon - One of the best experts on this subject based on the ideXlab platform.
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Effectiveness of Calcifediol in Improving Muscle Function in Post-Menopausal Women: A Prospective Cohort Study
Advances in therapy, 2017Co-Authors: G. Iolascon, Antimo Moretti, Alessandro De Sire, Dario Calafiore, Francesca GimiglianoAbstract:Introduction The role of vitamin D supplementation on muscle function and physical performance is still debated. Calcifediol is an available treatment for hypovitaminosis D, particularly for extra-skeletal effects. Aim of this prospective cohort study was to evaluate the effectiveness of Calcifediol on serum levels of 25(OH)D3, appendicular muscle strength, physical performance, and prevention of falls in post-menopausal women.
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P230 IS Calcifediol MORE EFFECTIVE THAN CHOLECALCIFEROL IN IMPROVING 25-HYDROXYVITAMIN D3 LEVELS, MUSCLE STRENGTH, AND PHYSICAL PERFORMANCE IN POSTMENOPAUSALWOMEN?
2016Co-Authors: Moretti A, A. De Sire, D. Calafiore, Gimigliano1 F. R. Gimigliano, G. IolasconAbstract:Objective: The aim of our study was to evaluate the effects of vitamin D on 25(OH)D3 levels, muscle strength, and physical performance in postmenopausal women, comparing Calcifediol and cholecalciferol. Material and Methods: In our real-practice study we included postmenopausal women aged ≥50 y; they were divided into two groups, according to the prescription: Calcifediol and cholecalciferol. We evaluated at the baseline (T0) and after six months (T1): serumlevels of 25(OH)D3, appendicular muscle strength, using the hand grip strength test (HGS) and the knee extensor strength test (KES), and physical performance, using the short physical performance battery (SPPB). Results: We evaluated 205 postmenopausal women, mean aged 69.28 ± 9.16 years, 103 treated with Calcifediol and 102 with cholecalciferol. In Table 1 we showed the results after vitamin D prescription. Table 1. Outcome measures assessed at the baseline and after 6 months of vitamin D supplementation. Calcifediol T0 (n = 103) Calcifediol T1 (n = 103) Pvalues 25(OH)D3 (ng/ml) 31.74 ± 13.03 51.80 ± 19.85
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Effects of Calcifediol versus cholecalciferol on 25(OH)D3 serum levels, appendicular muscle strength, and physical performance in post-menopausal women
2016Co-Authors: Moretti A, Alessandro De Sire, Dario Calafiore1, Raffaele Gimigliano, Francesca Gimigliano, G. IolasconAbstract:Background: Post-menopausal women generally present reduced serum levels of vitamin D, reduced VDR expression in skeletal muscle cells, and a gradual loss of muscle mass and muscle function. The relationship between serum 25-hydroxyvitamin D [25(OH)D3] levels and muscle strength has been extensively investigated, even though there is no agreement in literature. Therefore, aim of our study was to evaluate the effects of vitamin D on 25(OH)D3 levels, muscle strength, and physical performance in post-menopausal women, comparing Calcifediol and cholecalciferol. Material and methods: In this prospective study we included postmenopausal women, dividing them into two groups, according to the prescription performed (Calcifediol or cholecalciferol). We evaluated at the baseline (T0) and after 6 months (T1): serum levels of 25(OH)D3, appendicular muscle strength, using the Hand Grip Strength Test (HGS) and the Knee Extensor Strength Test (KES), and physical performance, using the Short Physical Performance Battery (SPPB). Results: We evaluated 205 post-menopausal women, mean aged 6928±916 years, 103 treated with Calcifediol and 102 with cholecalciferol. In Table 1 we showed the results. Table 1 Outcome measures assessed at the baseline and after 6 months of vitamin D supplementation. Calcifediol T0 (n=103) Calcifediol T1 (n=103) P values 25(OH)D3 (ng/ml) 31.74±13.03 51.80±19.85
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EFFECTS OF Calcifediol AND CHOLECALCIFEROL ON 25-HYDROXY-VITAMIN D3 LEVELS, MUSCLE STRENGTH, AND PHYSICAL PERFORMANCE IN POST-MENOPAUSAL WOMEN
2016Co-Authors: D. Calafiore, Moretti A, Francesca Gimigliano, Giamattei M. T., G. IolasconAbstract:Introduction/Background Post-menopausal women generally present reduced serum levels of vitamin D, reduced VDR expression in skeletal muscle cells, and a gradual loss of muscle mass and muscle function. The relationship between serum 25-hydroxyvitamin D [25(OH)D3] levels and muscle strength has been extensively investigated, even though there is no agreement in literature. Therefore, the objective of our study was to evaluate the effects of vitamin D on 25(OH)D3 levels, muscle strength, and physical performance in post-menopausal women, comparing Calcifediol and cholecalciferol. Material and Methods In our prospective study we included postmenopausal women aged ≥50 years, referring to our outpatient rehabilitation service for the prevention and management of osteoporosis. We divided our population into two groups, according to the prescription performed (Calcifediol or cholecalciferol). We evaluated at the baseline (T0) and after six months (T1): serum levels of 25(OH)D3, appendicular muscle strength, using the Hand Grip Strength Test (HGS) and the Knee Extensor Strength Test (KES), and physical performance, using the Short Physical Performance Battery (SPPB). Results We assessed 205 post-menopausal women, mean aged 69,28 ± 9,16 years; 103 treated with Calcifediol and 102 with cholecalciferol. In Table 1 we showed the differences in outcomes within groups. Conclusion Our results showed that post-menopausal women treated with Calcifediol had significant improvements in serum levels of 25(OH)D3, muscle strength, and physical performance
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114 EFFECTS OF Calcifediol AND CHOLECALCIFEROL ON 25-HYDROXY-VITAMIN D3 LEVELS, MUSCLE STRENGTH, AND PHYSICAL PERFORMANCE IN POST-MENOPAUSAL WOMEN
2016Co-Authors: D. Calafiore, Moretti A, Francesca Gimigliano, Giamattei M. T., G. IolasconAbstract:Introduction/Background Post-menopausal women generally present reduced serum levels of vitamin D, reduced VDR expression in skeletal muscle cells, and a gradual loss of muscle mass and muscle function. The relationship between serum 25-hydroxyvitamin D [25(OH)D3] levels and muscle strength has been extensively investigated, even though there is no agreement in literature. Therefore, the objective of our study was to evaluate the effects of vitamin D on 25(OH)D3 levels, muscle strength, and physical performance in post-menopausal women, comparing Calcifediol and cholecalciferol. Material and Methods In our prospective study we included postmenopausal women aged ≥50 years, referring to our outpatient rehabilitation service for the prevention and management of osteoporosis. We divided our population into two groups, according to the prescription performed (Calcifediol or cholecalciferol). We evaluated at the baseline (T0) and after six months (T1): serum levels of 25(OH)D3, appendicular muscle strength, using the Hand Grip Strength Test (HGS) and the Knee Extensor Strength Test (KES), and physical performance, using the Short Physical Performance Battery (SPPB). Results We assessed 205 post-menopausal women, mean aged 69,28 ± 9,16 years; 103 treated with Calcifediol and 102 with cholecalciferol. In Table 1 we showed the differences in outcomes within groups. Conclusion Our results showed that post-menopausal women treated with Calcifediol had significant improvements in serum levels of 25(OH)D3, muscle strength, and physical performance
Mario Cozzolino - One of the best experts on this subject based on the ideXlab platform.
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evaluating extended release Calcifediol as a treatment option for chronic kidney disease mineral and bone disorder ckd mbd
Expert Opinion on Pharmacotherapy, 2019Co-Authors: Mario Cozzolino, Markus KettelerAbstract:ABSTRACTIntroduction: Extended-release Calcifediol (ERC) is an orally administered prohormone of active vitamin D (1,25-dihydroxyvitamin D [1,25D]) designed to safely and sufficiently increase seru...
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Calcifediol to treat secondary hyperparathyroidism in patients with chronic kidney disease.
Expert review of clinical pharmacology, 2017Co-Authors: Andrea Galassi, Antonio Bellasi, Paola Ciceri, Francesca Pivari, Ferruccio Conte, Mario CozzolinoAbstract:Deranged vitamin D metabolism represents an active trigger of secondary hyperparathyroidism (SHPT) in CKD. Correction of 25(OH)D deficiency by nutritional Vitamin D administration is suggested by KDIGO guidelines, to prevent and treat SHPT in CKD stage G3-G5 and G1T-G5T patients, although with a still inconsistent background. Nutritional vitamin D is available as cholecalciferol, ergocalciferol, or Calcifediol. Superiority of Calcifediol in increasing 25(OH)D levels has been suggested due to its better bioavailability. The safer pharmacokinetic of the recent modified-release (MR) formulation of Calcifediol was effective in replenishing 25(OH)D levels with minimal impact on vitamin D catabolism and fibroblast-growth factor-23 (FGF-23) activation. Areas covered: the review discusses utility of Calcifediol for treating SHPT in different CKD stages under physiology driven approach, focusing on vitamin D metabolism, guidelines suggestions and comparison between clinical effects on SHPT elicited by Calcifediol, cholecalciferol and ergocalciferol. Expert commentary: although optimal targets of 25(OH)D and parathormone remain uncertain, Calcifediol, especially in its newer MR formulation, may represent an intriguing option to combine an efficacious correction of 25(OH)D deficit and SHPT, with a limited impact on vitamin D catabolism and FGF-23 activation. Newer data are required to better explore the role of MR Calcifediol in treating SHPT.
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Vitamin D in patients with chronic kidney disease: a position statement of the Working Group “Trace Elements and Mineral Metabolism” of the Italian Society of Nephrology
Journal of Nephrology, 2016Co-Authors: Luigi Francesco Morrone, Andrea Galassi, Sandro Mazzaferro, Pergiorgio Bolasco, Corrado Camerini, Giuseppe Cianciolo, Adamasco Cupisti, Domenico Russo, Luigi Russo, Mario CozzolinoAbstract:In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of Calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (Calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians.
Fen-er Chen - One of the best experts on this subject based on the ideXlab platform.
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Asymmetric Synthesis of Vitamin D3 Analogues: Organocatalytic Desymmetrization Approach toward the A-Ring Precursor of Calcifediol.
Organic letters, 2015Co-Authors: Haifeng Wang, Linjie Yan, Fen-er ChenAbstract:A novel asymmetric synthesis has been developed for the construction of the A-ring of a chiral precursor to Calcifediol. The highlights of this synthesis include (i) the introduction of the stereochemistry at the C5-position of the A-ring through the organocatalytic enantioselective desymmetrization of a prochiral cyclic anhydride using a bifunctional urea catalyst and (ii) the introduction of the exo-cyclic (Z)-dienol side chain by a tandem Claisen rearrangement/sulfoxide thermolysis of an allylic alcohol.
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Asymmetric Synthesis of Vitamin D3 Analogues: Organocatalytic Desymmetrization Approach toward the A‑Ring Precursor of Calcifediol
2015Co-Authors: Haifeng Wang, Linjie Yan, Fen-er ChenAbstract:A novel asymmetric synthesis has been developed for the construction of the A-ring of a chiral precursor to Calcifediol. The highlights of this synthesis include (i) the introduction of the stereochemistry at the C5-position of the A-ring through the organocatalytic enantioselective desymmetrization of a prochiral cyclic anhydride using a bifunctional urea catalyst and (ii) the introduction of the exo-cyclic (Z)-dienol side chain by a tandem Claisen rearrangement/sulfoxide thermolysis of an allylic alcohol
Andreas Egli - One of the best experts on this subject based on the ideXlab platform.
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Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial
JAMA internal medicine, 2016Co-Authors: Heike A. Bischoff-ferrari, Bess Dawson-hughes, Hannes B. Staehelin, Robert Theiler, E. John Orav, Otto W. Meyer, W. Dick, Walter C. Willett, Andreas EgliAbstract:Importance Vitamin D deficiency has been associated with poor physical performance. Objective To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. Interventions Three study groups with monthly treatments, including a low-dose control group receiving 24 000 IU of vitamin D 3 (24 000 IU group), a group receiving 60 000 IU of vitamin D 3 (60 000 IU group), and a group receiving 24 000 IU of vitamin D 3 plus 300 μg of Calcifediol (24 000 IU plus Calcifediol group). Main Outcomes and Measures The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index. Results The study cohort comprised 200 participants (men and women ≥70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient ( P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups ( P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60 000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24 000 IU plus Calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24 000 IU group (47.9%; 95% CI, 35.8%-60.3%) ( P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60 000 IU group (mean, 1.47) and the 24 000 IU plus Calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24 000 IU group (mean, 0.94) ( P = .09). Conclusions and Relevance Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24 000 IU. Trial Registration clinicaltrials.gov Identifier:NCT01017354
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Calcifediol Versus Vitamin D3 Effects on Gait Speed and Trunk Sway in Young Postmenopausal Women: A Double-Blind Randomized Controlled Trial
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteopor, 2014Co-Authors: Otto Meyer, Andreas Egli, Bess Dawson-hughes, Hannes B. Staehelin, E. Sidelnikov, D. Grob, G. Theiler, Reto W. Kressig, H.-p. Simmen, Robert TheilerAbstract:Summary In this double-blind RCT, 4-month treatment with Calcifediol compared with vitamin D3 improved gait speed by 18 % among young postmenopausal women. Consistently, change in 25(OH)D blood levels over time were significantly correlated with improvement in gait speed in these women. No effect could be demonstrated for trunk sway.
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Pharmacokinetics of oral vitamin D3 and Calcifediol
Bone, 2014Co-Authors: Alexander Jetter, Andreas Egli, Bess Dawson-hughes, Hannes B. Staehelin, Elisabeth Stoecklin, Richard Goessl, Jana Henschkowski, Heike A. Bischoff-ferrariAbstract:Abstract Aim Long-term pharmacokinetics after supplementation with vitamin D 3 or Calcifediol (the 25-hydroxyvitamin D 3 metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D 3 or Calcifediol lead to 25(OH)D 3 plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D 3 during different vitamin D 3 and Calcifediol supplementation regimens. Methods In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70 years (5 per group) received 20 μg Calcifediol or vitaminD 3 daily, 140 μg Calcifediol or vitaminD 3 weekly, for 15 weeks, or a single bolus of either 140 μg Calcifediol, or vitaminD 3 , or both. 25(OH)D 3 plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants. Results For daily (weekly) dosing, the area under the concentration–time curve (AUC 0–24h ), which is the measure for exposure, was 28% (67%) higher after the first dose of Calcifediol than after the first dose of vitamin D 3 . After 15 weeks, this difference was 123% (178%). All women in the daily and weekly Calcifediol groups achieved 25(OH)D 3 concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D 3 daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg Calcifediol led to 117% higher 25(OH)D 3 AUC 0–96h values than 140 μg vitamin D 3 , while the simultaneous intake of both did not further increase exposure. Conclusions Calcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D 3 concentrations than vitamin D 3 . Plasma 25(OH)D 3 concentrations of 30 ng/mL were reached more rapidly and reliably with Calcifediol.