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Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule.

ABSTRACT: Vitamin D deficiency is frequent in the general population and both subjects and health professionals could benefit from a broader range of vitamin D3 formulations. We conducted a single-dose, open-label, parallel-group, randomized bioequivalence study to compare a single dose of a newly developed vitamin D3 100,000 IU in a soft capsule (Group 1) with the reference drug vitamin D3 100,000 IU oral solution in ampoule (Group 2) in healthy volunteers over a four-month period. The primary endpoint was the area under the curve (AUC) of serum 25-hydroxyvitamin-D (25(OH)D) concentrations on Day 112. This study was conducted in France from February to June 2014 in 53 young adults with a mean age of 26.9 years. At baseline, low mean serum 25(OH)D levels were observed in both groups (10.6 ng/mL in Group 1 and 9.0 ng/mL in Group 2). On Day 112, the AUC of serum 25(OH)D concentration was 2499.4 ± 463.8 nmol/mL (7.8 ± 0.2 for LogAUC) for Group 1 and 2152.3 ± 479.8 nmol/mL (7.6 ± 0.2 for LogAUC) for Group 2. Bioequivalence of the two treatments was not demonstrated. Superiority of vitamin D3 100,000 IU soft capsule was observed with p = 0.029 for AUC and p = 0.03 for LogAUC using a non-parametric Wilcoxon test. The profile of the serum 25(OH)D concentration showed a significant difference in favor of Group 1 on Days 1, 3, 7, 14 and 90. Mean serum 25(OH)D concentrations in Group 1 were between 20 and 30 ng/mL during the four-month period and under 20 ng/mL throughout the study in Group 2, except on Day 112. Mean Cmax for Group 1 was significantly higher (p = 0.002). Fourteen days were needed to reach Tmax by more than half the subjects in Group 1 compared to 45 days in Group 2. Both treatments were well tolerated, with no severe or related adverse events reported. In conclusion, the pharmacokinetic profile of the new formulation of vitamin D3 100,000 IU soft capsule is superior to that of the oral solution in ampoule. The new formulation increased serum 25(OH)D levels to above 20 ng/mL and maintained levels from 20 ng/mL to 30 ng/mL for four months in late winter and spring.

SUBMITTER: Mentaverri R

PROVIDER: S-EPMC6470992 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule.

Mentaverri Romuald R Souberbielle Jean-Claude JC Brami Gilles G Daniel Christelle C Fardellone Patrice P

Nutrients 20190326 3

Vitamin D deficiency is frequent in the general population and both subjects and health professionals could benefit from a broader range of vitamin D3 formulations. We conducted a single-dose, open-label, parallel-group, randomized bioequivalence study to compare a single dose of a newly developed vitamin D3 100,000 IU in a soft capsule (Group 1) with the reference drug vitamin D3 100,000 IU oral solution in ampoule (Group 2) in healthy volunteers over a four-month period. The primary endpoint w ...[more]

PMID: 30917531

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Project description:Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

Project description:BACKGROUND:The appropriate dose of vitamin D supplementation in children is still debated. We calculated that the recommended dose of 600-1000?IU vitamin D3/day is not sufficient to reach a serum 25-hydroxyvitamin D (25-OH-D) level of at least 30?ng/ml (75?nmol/l) in north Italian children >?12?months. The aim of this study was to analyse the effect of seasonal supplementation with 1500?IU (=37.5??g) vitamin D3/day. METHODS:DINOS (D-vitamIN Oral Supplementation) study was a pilot, monocentric, non-random case-control register study. It was conducted in a paediatric primary care setting near Padova (North Italy, 45°N latitude). The data of 203 children (girls:boys 1:1,33) aged 2-15?years, collected between November 2010 and January 2015, were analysed. Active group A (n?=?82) were given 1500?IU vitamin D3/day from November to April; control Group B (n?=?121) received no supplementation. The serum 25-OH-D test was part of a laboratory tests panel and performed using a chemiluminescence immunoassay method. RESULTS:Serum 25-OH-D mean level + standard deviation throughout the period was 32 + 13?ng/ml (80 + 32?nmol/l) in group A vs 22 + 10?ng/ml (55 + 25?nmol/l) in group B. In group A 12% had vitamin D deficiency 25-OH-D?<?20?ng/ml (50?nmol/l) and 1.2% severe vitamin D deficiency 25-OH-D?<?10?ng/ml (25?nmol/l). In group B 46% had vitamin D deficiency and 9% severe deficiency (P?<? 0.001). In group A mean levels were normal or near-normal all the year except in May. Group B reached mean 25-OH-D levels close to 30?ng/ml (75?nmol/l) only in late summer. The active group mean 25-OH-D level was normal in preschoolers and schoolers but not in adolescents. Non-white children had a three-times vitamin D deficiency probability despite supplementation. CONCLUSIONS:Vitamin D supplementation with at least 1500?IU vitamin D3/day from November to April was found appropriate for children in North Italy. A prolongation until May could be useful. Higher doses and/or prolonged periods could be more appropriate especially in adolescents and in non-white children. STUDY REGISTRATION:DINOS gained the approval of Padova Ethics Committee (n. 3960/U16/2016).

Project description:Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Project description:BackgroundNew evidence supports the use of supplemental vitamin D in the prevention of exacerbation of asthma; however, the optimal posology to sufficiently raise serum levels while maximising adherence is unclear. The objective was to ascertain the efficacy of high-dose vitamin D3 in increasing serum vitamin D in preschoolers with asthma and provide preliminary data on safety and efficacy outcomes.MethodsWe conducted a 7-month, triple-blind, randomised, placebo-controlled, pilot trial of children aged 1-5 years with viral-induced asthma. Participants were allocated to receive two oral doses of 100,000 IU vitamin D3 (intervention) or identical placebo (control) 3.5 months apart, once in the fall and once in the winter. Serum 25-hydroxyvitamin D (25OHD) was measured by tandem mass spectrometry at baseline, 10 days, 3.5 months, 3.5 months + 10 days, and 7 months. The main outcome was the change in serum 25OHD from baseline (Δ25OHD) over time and at 3.5 and 7 months; other outcomes included the proportion of children with 25OHD ≥ 75 nmol/L, safety, and adverse event rates.ResultsChildren (N = 47) were randomised (intervention, 23; control, 24) in the fall. There was a significant adjusted group difference in the Δ25OHD (95% confidence interval) of 57.8 (47.3, 68.4) nmol/L, p < 0.0001), with a time (p < 0.0001) and group*time interaction effect (p < 0.0001), in favour of the intervention. A significant group difference in the Δ25OHD was observed 10 days after the first (119.3 [105.8, 132.9] nmol/L) and second (100.1 [85.7, 114.6] nmol/L) bolus; it did not reach statistical significance at 3.5 and 7 months. At 3.5 and 7 months, respectively, 63% and 56% of the intervention group were vitamin D sufficient (≥ 75 nmol/L) compared to 39% and 36% of the control group. Hypercalciuria, all without hypercalcaemia, was observed in 8.7% of intervention and 10.3% of control samples at any time point. Exacerbations requiring rescue oral corticosteroids, which appear as a promising primary outcome, occurred at a rate of 0.87/child.ConclusionTwo oral boluses of 100,000 IU vitamin D3,once in the fall and once in the winter, rapidly, safely, and significantly raises overall serum vitamin D metabolites. However, it is sufficient to maintain 25OHD ≥ 75 nmol/L throughout 7 months in only slightly more than half of participants.Trial registrationClinicalTrials.gov, NCT02197702 (23 072014). Registered on 23 July 2014.

Project description:BackgroundVitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied.ObjectiveWe aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults.MethodsIn study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2.ResultsIn study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported.ConclusionOur results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions.Clinical trial registrationclinicaltrials.gov, identifier: NCT05706259.

Project description:BACKGROUND:Low 25-hydroxyvitamin D (25OHD) levels (<?75 nmol/l) are inversely associated with anemia prevalence. Since anemia and low 25OHD levels are common in patients with heart failure (HF), we aimed to investigate whether vitamin D supplementation can reduce anemia prevalence in advanced HF. METHODS:EVITA (Effect of Vitamin D on Mortality in Heart Failure) is a randomized, placebo-controlled clinical trial in patients with initial 25OHD levels <?75 nmol/l. Participants received either 4000 IU vitamin D3 daily or a matching placebo for 36 months. A total of 172 patients (vitamin D group: n?=?85; placebo group: n?=?87) were investigated in this pre-specified secondary data analysis. Hemoglobin (Hb) and other hematological parameters were measured at baseline and study termination. Assessment of between-group differences in anemia prevalence and Hb concentrations was performed at study termination, while adjusting for baseline differences. RESULTS:In the vitamin D and placebo group, baseline proportions of patients with anemia (Hb?<?12.0 g/dL in females and <?13.0 g/dL in males) were 17.2% and 10.6%, respectively (P?=?0.19). At study termination, the proportion of patients with anemia in the vitamin D and placebo groups was 32.2% and 31.8%, respectively (P?>?0.99). There was no between-group difference in change in the Hb concentrations (-?0.04 g/dL [95%CI:-0.53 to 0.45 g/dL]; P?=?0.87). Results regarding anemia risk and Hb concentrations were similar in the subgroup of patients with chronic kidney disease (vitamin D group: n?=?26; placebo group: n?=?23). Moreover, results did not differ substantially when data analysis was restricted to patients with deficient baseline 25OHD levels. CONCLUSIONS:A daily vitamin D supplement of 4000 IU did not reduce anemia prevalence in patients with advanced HF. Data challenge the clinical relevance of vitamin D supplementation to increase Hb levels. TRIAL REGISTRATION:The study was registered at EudraCT (No. 2010-020793-42) and clinicaltrials.gov ( NCT01326650 ).

Dataset Information

Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule.

Publications

Pharmacokinetics of a New Pharmaceutical Form of Vitamin D3 100,000 IU in Soft Capsule.

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