Pharmacokinetics of Oral Cholecalciferol in Healthy Subjects with Vitamin D Deficiency: A Randomized Open-Label Study

Background: The aim of this study was to investigate the pharmacokinetic (PK) and safety profile of high-dose vitamin D supplementation, comparing different schedules (daily, weekly, or bi-weekly) in an otherwise healthy vitamin D-deficient population. Methods: Single-center, open-label study on healthy subjects deficient in vitamin D (25 (OH)D < 20 ng/mL), randomized to receive cholecalciferol (DIBASE®, Abiogen Pharma, Italy) using three different schedules: Group A: 10,000 IU/day for eight weeks followed by 1000 IU/day for four weeks; Group B: 50,000 IU/week for 12 weeks, Group C: 100,000 IU/every other week for 12 weeks. Total cumulative doses were: 588,000 IU, 600,000 IU, 600,000 IU. The treatment regimens corresponded to the highest doses allowed for cholecalciferol for the correction of vitamin D deficiency in adults in Italy. Results: mean 25 (OH)D plasma levels significantly increased from baseline 13.5 ± 3.7 ng/mL to peak values of 81.0 ± 15.0 ng/mL in Group A, 63.6 ± 7.9 ng/mL in Group B and 59.4 ± 12 ng/mL in Group C. On day 28, all subjects showed 25 (OH)D levels ≥20 ng/mL and 93.1% had 25 (OH)D levels ≥30 ng/mL. On day 56 and 84, all subjects had 25 (OH)D levels ≥30 ng/mL. No serious adverse events occurred during the study. Conclusions: normalization of 25 (OH)D serum levels was quickly attained with all the studied regimens. A more refracted schedule provided a higher systemic 25 (OH)D exposure.

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A RANDOMISED, PROSPECTIVE, PARALLELAND OPEN LABEL STUDY TO COMPARE EFFICACY AND SAFETY OF METFORMIN PLUS ROSUVASTATIN AND GLIMEPIRIDE PLUS ROSUVASTATIN IN PATIENTS OF COEXISTING NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND TYPE 2 DIABETES MELLITUS (T2DM)

10.36106/ijsr/3101504 ◽

2021 ◽

pp. 46-49

Author(s):

Prabhsimran kaur ◽

Gurpreet Kaur Randhawa ◽

Surinder Kumar Salwan

Keyword(s):

Insulin Resistance ◽

Treatment Options ◽

Antidiabetic Drugs ◽

Open Label ◽

Alcoholic Fatty Liver ◽

Open Label Study ◽

Label Study ◽

Group A ◽

Group B ◽

Lipid Parameters

Background and Objectives: NAFLD and T2DM has global prevalence of 55.5% with currently no approved treatment. There is insufcient data for its pharmacotherapy. The sharing of risk factors, most common being the insulin resistance between NAFLD and T2DM, makes the antidiabetic drugs, with effect on insulin resistance, the potential treatment options. The aim was to compare efcacy and safety of antidiabetic drugs i.e. Metformin and Glimepiride with concomitant Rosuvastatin in NAFLD coexistent with T2DM. Methods: Randomized, prospective, parallel and open-label study recruited 60 patients of concomitant NAFLD and T2DM after getting Institutional Review Board approval. Patients of either sex (20-60 years) with NAFLD (ultrasound diagnosed & raised AST 50-150 U/L) and T2DM(FBS> 126mg/dl) were recruited in medicine OPD after obtaining written informed consent. Chronic alcohol users and pregnancy cases were excluded. Patients were randomised into Group A[Rosuvastatin(10mg OD)+ Metformin(1gm BD)] & Group B[Rosuvastatin(10mg OD)+Glimepiride(3mg BD)]. Primary outcome was improvement in hepatic parameters and ultrasound grading of liver. Secondary outcomes were improvement in anthropometric, glycaemic and lipid parameters and assessment of safety. Results: Group A caused signicant(p<0.05) reduction in hepatic parameters(S.Bilirubin & AST). Group A and B showed non-signicant improvement(p>0.05) in ultrasound grading of liver, respectively (24% vs 20% patients). Intergroup difference was signicant(p<0.05) for weight and BMI in Group A. Both groups showed highly signicant(p<0.001) reduction in glycaemic parameters and signicant(p<0.05) reduction in lipid parameters. Both treatments were safe. Conclusion: Metformin plus Rosuvastatin seems to be more efcacious in NAFLD and T2DM over 90 days. These drugs could improve prognosis because of insulin sensitising action and additional benets in cancers, cardiovascular diseases. Further studies are required to strengthen these ndings which may help in nding a standard treatment for NAFLD and T2DM.

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Impact of the 25-Hydroxycholecalciferol Concentration and Vitamin D Deficiency Treatment on Changes in the Bone Level at the Implant Site during the Process of Osseointegration: A Prospective, Randomized, Controlled Clinical Trial

Journal of Clinical Medicine ◽

10.3390/jcm10030526 ◽

2021 ◽

Vol 10 (3) ◽

pp. 526

Author(s):

Jakub Kwiatek ◽

Aleksandra Jaroń ◽

Grzegorz Trybek

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Controlled Clinical Trial ◽

Randomized Controlled ◽

Group A ◽

Bone Level ◽

Group B ◽

Implant Treatment ◽

Correct Level ◽

25 Hydroxycholecalciferol

Introduction: The most important factor which is responsible for the positive course of implant treatment is the process of osseointegration between the implant structure and the host’s bone tissue. The aim of this study was to assess what effect the 25-hydroxycholecalciferol concentration and vitamin D deficiency treatment have on changes in the bone level at the implant site during the process of osseointegration in the mandible. Materials and Methods: The study was with 122 people qualified for implant surgery, who were assigned to three research groups (A, B, and C). Laboratory, clinical, and radiological tests were performed on the day of surgery, and after 6 and 12 weeks. The bone level in the immediate proximity of the implant was determined by radiovisiography (RVG). Results: The bone level after 12 weeks in Groups B and C was significantly higher than after 6 weeks. The bone level in the study Group B was significantly higher than in Group A. The study showed that the higher the levels of 25-hydroxycholecalciferol were observed on the day of surgery, the higher was the level of bone surrounding the implant after 6 and 12 after surgery. Conclusion: The correct level of 25-hydroxycholecalciferol on the day of surgery and vitamin D deficiency treatment significantly increase the bone level at the implant site in the process of radiologically assessed osseointegration.

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Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Metabolites ◽

10.3390/metabo11050276 ◽

2021 ◽

Vol 11 (5) ◽

pp. 276

Author(s):

Stefania Raimondo ◽

Dragana Nikolic ◽

Alice Conigliaro ◽

Gianluca Giavaresi ◽

Bruna Lo Sasso ◽

...

Keyword(s):

Risk Factors ◽

Healthy Subjects ◽

Cardiometabolic Risk ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Modifiable Risk Factors ◽

Low Density Lipoprotein Cholesterol ◽

Open Label ◽

Open Label Study ◽

Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.

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An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function

Clinical Pharmacology in Drug Development ◽

10.1002/cpdd.149 ◽

2014 ◽

Vol 4 (4) ◽

pp. 256-261 ◽

Cited By ~ 6

Author(s):

Franklin K. Johnson ◽

Paul N. Mudd ◽

Tara DiMino ◽

Jennie Vosk ◽

Sheela Sitaraman ◽

...

Keyword(s):

Renal Function ◽

Normal Renal Function ◽

Healthy Subjects ◽

Impaired Renal Function ◽

Open Label ◽

Open Label Study ◽

Label Study

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High-Dose Terazosin Therapy (5 mg) in Korean Patients with Lower Urinary Tract Symptoms with or without Concomitant Hypertension: A Prospective, Open-Label Study

Yonsei Medical Journal ◽

10.3349/ymj.2007.48.6.994 ◽

2007 ◽

Vol 48 (6) ◽

pp. 994 ◽

Cited By ~ 1

Author(s):

Cheol Kwak ◽

Jeong Ki Lee ◽

Ja Hyeon Ku

Keyword(s):

Urinary Tract ◽

Lower Urinary Tract Symptoms ◽

Lower Urinary Tract ◽

High Dose ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Urinary Tract Symptoms ◽

Concomitant Hypertension ◽

Lower Urinary

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Clinical efficacy of different dosage forms containing vitamin D: design and study outcomes of a randomized, comparative clinical trial

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20203104 ◽

2020 ◽

Vol 7 (3) ◽

pp. 176

Author(s):

Nidhi Sapkal ◽

Gaurav Chhaya ◽

Milan Satya ◽

Dhara Shah

Keyword(s):

Vitamin D ◽

Clinical Efficacy ◽

Dosage Forms ◽

Oral Solution ◽

Blood Levels ◽

Open Label ◽

Soft Gelatin Capsules ◽

25 Hydroxy Vitamin D ◽

Group A ◽

Group B

Background: Different dosage forms of vitamin D like tablets, soft gelatin capsules, oral granules, powders, solutions and thin films are available. The objective of the present study was to evaluate and compare the clinical efficacy of three different dosage forms of vitamin D3 namely, orally disintegrating strips, oral granules and oral solution.Methods: An open label, single centre, prospective, randomized, parallel group, comparative study was conducted for a period of 4 months. The study participants were divided into three groups (A, B, C) and received the respective treatments (orally disintegrating strips, n=20; granules, n=20; oral nano solution, n=10) for the study period. The estimation of blood levels of 25-hydroxy vitamin D [25(OH)D3] in all the subjects at day 0, 60 and 120 was carried out.Results: The normalization level of 25(OH)D3 achieved by the subjects in group A, group B and group C was 100%, 83.3% and 90% respectively after 90 days. Comparison of 25(OH)D3 level in all three groups showed significant increase at day 60. The levels were maintained at day 90 and 120 even after drastic reduction in dosage in Group A and group C. On day 120, the dose reduction was in the order of group A>group C>group B.Conclusions: All the three formulations showed increase in the level of 25(OH)D3. It can be concluded that oral disintegrating strips of 25(OH)D3 are clinically more efficient than other conventional dosage forms.

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Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00008-07 ◽

2007 ◽

Vol 51 (8) ◽

pp. 2982-2984 ◽

Cited By ~ 4

Author(s):

Mary B. Wire ◽

Charles H. Ballow ◽

Julie Borland ◽

Mark J. Shelton ◽

Yu Lou ◽

...

Keyword(s):

Steady State ◽

Healthy Subjects ◽

Open Label ◽

Time Curve ◽

Once Daily ◽

Open Label Study ◽

Label Study ◽

Concentration Time

ABSTRACT Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

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P–662 Study on D-vitamin, AMH and insulin interrelation in Polycystic Ovary Syndrome (PCOS) patients

Human Reproduction ◽

10.1093/humrep/deab130.661 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

A Coc. Lizarraga ◽

S Lindenberg ◽

G Juu. Almind ◽

F Lindenberg

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Serum Vitamin ◽

Serum Vitamin D ◽

Vitamin D Levels ◽

Group A ◽

D Values ◽

Group B

Abstract Study question Is vitamin D deficiency more prevalent in PCOS patients? Is there a link between vitamin D levels and metabolic status in PCOS subjects? Summary answer An inverse relationship between vitamin D levels and metabolic status was demonstrated and it is thought to be responsible of its pathogenesis. What is known already PCOS is a multifactorial condition, characterised by failure in oogenesis and anovulation. Obesity is a common condition linked to its clinical features and studies have reported inverse associations between BMI and severity of the condition. Furthermore, 67–85% of PCOS patients have vitamin D deficiency. Low levels of vitamin D have been found to be closely related to insulin resistance, obesity, or hyperandrogenism and there is a significant association between serum vitamin D levels and reproductive function. Other factors such as AMH have also been described as possibly involved in the pathophysiology. Study design, size, duration We performed a retrospective, analytical and observational study in the Copenhagen Fertility Center. Patients referred with cycle abnormalities, hirsutism, and infertility were evaluated. A total of 778 women were enrolled consecutively from January 2019 to October 2020. Subjects who had major medical disorders were excluded. We selected those in which vitamin D was measured in the baseline analysis selecting a total of 396 patients. The further analysis has been carried out from 100 randomly selected patients. Participants/materials, setting, methods Blood samples were drawn after overnight fasting. They were all assayed in the same laboratory. Biochemical parameters were analyzed using descriptive statistics. Same parameters were studied after dividing into vitamin D deficiency group or optimal levels using a multiple t-test. Correlation between variables was determined. Graphpad Prism program version 8 was used to perform the calculations. The level of statistical significance was set at P-value < 0.05. Main results and the role of chance A total of 100 subjects fulfilling the inclusion criteria were selected randomly from 396 PCOS women. Serum vitamin D concentrations were highly variable ranging from 16 nmol/L to 175 nmol/L. The prevalence of vitamin D deficiency was 24% and 41% of the subjects were classified as vitamin D insufficient. Only 35% of our patients had optimal vitamin D values. We compared data between the group with optimal values of vitamin D (Group A) versus the group with insufficient/deficient vitamin D values (Group B). We found statistical difference between groups in PTH values, being notably higher in group B compared with group A. Despite no statistically significant difference was obtained, it is important to highlight that the mean of SHBG was lower in group B and the mean of androstenedione, AMH, FAI and HOMA-IR were much higher in this group as well. Following the HOMA-IR criteria, 55% of patients had insulin resistance. Specifically, 26% had moderate insulin resistance and 29% severe insulin resistance. Levels of vitamin D were negatively correlated with FAI, AMH and HOMA-IR and positively correlated with HDL-Cholesterol and SHBG. Statistically significant differences were evidenced in the correlation between vitamin D and FAI and SHBG. Limitations, reasons for caution This is a retrospective observational study on a consecutive admitted patient group with a lack of a control group. Another limitation is the small sample size. It is difficult to generalize with other degrees of severity. We didn’t assess seasonal variability or if they were taking any vitamin D supplementation. Wider implications of the findings: Properly randomized clinical trials are mandatory to achieve more conclusive results about the role of vitamin D. Available evidence is promising but not sufficient to draw final conclusions. The aim is to better understand the pathophysiology of the condition and the factors involved and to find new target treatments. Trial registration number 1

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Is There a Relationship Between Vitamin D Deficiency Status and PCOS in Infertile Women?

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0871-6831 ◽

2019 ◽

Vol 79 (07) ◽

pp. 723-730 ◽

Cited By ~ 2

Author(s):

Emine Arslan ◽

Umit Gorkem ◽

Cihan Togrul

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Polycystic Ovary ◽

Total Testosterone ◽

Anthropometric Parameters ◽

Infertile Women ◽

Vitamin D Levels ◽

Pcos Group ◽

Group A ◽

Group B

Abstract Introduction It is still unclear in the literature whether low vitamin D levels play a role in the pathogenesis of polycystic ovary syndrome (PCOS), especially with respect to the regulation of anti-Müllerian hormone (AMH). Therefore, we aimed to investigate whether there could be a relationship between vitamin D deficiency status and PCOS. Materials and Methods A total of 146 infertile women were divided into two groups according to their ovarian reserve patterns: (i) normal (NOR), and (ii) high (PCOS). The participants were also categorized into two groups according to vitamin D concentrations: (i) Group A < 10 ng/mL, and (ii) Group B 10 – 20 ng/mL. Samples were obtained and analyzed for estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S) and AMH. Results In the NOR group, there were significant differences between Group A and Group B in terms of anthropometric characteristics (p < 0.05, for all). The women in both Group A and Group B had similar AMH concentrations (p > 0.005). Only the NOR group showed a significant though moderate negative correlation between 25(OH)D levels and anthropometric parameters. AMH levels were not correlated with 25(OH)D levels in the NOR or the PCOS group (r = − 0.112, p = 0.008; r = 0.027, p = 0.836). Multivariate regression analysis showed no impact of 25(OH)D on other study parameters. Only AMH measurements were significant enough (p < 0.001) to differentiate between PCOS and NOR patterns. Conclusion We found no difference in serum 25(OH)D and AMH levels between women with and women without PCOS. No correlation could be demonstrated between 25(OH)D and AMH in the PCOS group or controls.

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