Population pharmacokinetics of 25-hydroxyvitamin D in healthy young adults.

OBJECTIVES: The aim of our study was to develop a population pharmacokinetic (PPK) model for 25-hydroxyvitamin D clearance in a healthy young adult population in Serbia. METHODS: Study sample consisted of 70 healthy young students of the Faculty of Medical Science, University of Kragujevac, Serbia, with a mean age and body mass index of 22.39 ± 1.82 years and 21.31 ± 2.69 kgm-2, respectively. Non-linear mixed-effect modeling (NONMEM) software was used for data analysis. A validation set of 16 participants was used to estimate the predictive performance of the pharmacokinetic model. RESULTS: In the base model (without covariates), we had parameter estimates of 0.01 L/h for apparent clearance, 0.25 L for apparent volume of distribution, while value of minimum objective function (MOF) was 383.468. The full regression model was established by estimating the effects of 12 covariates. Mean intake of vitamin D from foods (DD) and value of phosphate in serum (PHO) were covariates included in the final model, while others were excluded in this process. The estimated value in the final MOF model was 274.555. The final regression model formula was: clearance (CL) (L/h) = 0.0711 + 0.738 x DD + 0.618 x PHO. CONCLUSIONS: The PPK model obtained determined clearance of 25-hydroxyvitamin D in a healthy young adult population in Serbia. Mean intake of vitamin D from foods and serum phosphate level are the most important covariates that influence value of 25-hydroxyvitamin D clearance in healthy young adults.

The influence of vitamin D supplementation on the expression of mediators of inflammation in knee osteoarthritis.

This trial aimed to determine the possible therapeutic and immunomodulatory effects of vitamin D3 in patients with knee OA. In this open-label clinical trial, symptoms were assessed over 3 months in patients with primary knee OA receiving oral vitamin D3 4000 IU/day. Clinical response was evaluated at baseline and 3 months using WOMAC subscores and VAS. Serum levels of cytokines IL-1ß, TNF-α, IL-13, IL-17, IL-33, IL-4, and IL-10 were determined by ELISA method. Eighty patients with knee OA were included. All 80 completed the study; the median 25(OH)D3 level was 23.1 ng/ml at baseline and increased by 12.3 ng/ml after treatment. Vitamin D3 after 3 months of supplementation induced a significant reduction in VAS pain and WOMAC subscores. Using OMERACT-OARSI criteria, 86.7% of patients treated with vitamin D3 responded to treatment. At the end of 3 months, systemic values of IL-1ß (p < 0.01), IL-23 (p < 0.01), and IL-33 (p < 0.01) were significantly increased, values of TNF-α (p < 0.01), IL-13 (p < 0.01), and IL-17 (p < 0.01) were significantly decreased, while value of IL-4 was not significantly changed. No adverse events were detected. Treatment with vitamin D is associated with improvement in pain, as well as stiffness and physical function. Vitamin D supplementation increased systemic values of IL-33. Our results indicate that vitamin D3 supplementation may be used as a novel therapeutic in knee OA. Future studies are needed to investigate a potential role of IL-33 in the pathogenesis of knee OA.

Granulomatosis with polyangitis (Wegener's) and central nervous system involvement: case report.

INTRODUCTION: Granulomatosis with polyangitis (Wegener's) is an antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, which commonly involves the upper and lower respiratory tracts and kidneys. Central nervous system involvement is reported in less than 11%, and rarely present at onset. CASE OUTLINE: We report the case of a 41-year-old male patient with a high disease activity, large organ involvement, as well as central nervous system manifestations presented at onset.Treatment with intravenous pulse methylprednisolone, followed by the pulsed doses of cyclophosphamide was induced. After 6 months of cyclophosphamide pulse therapy a remission was achieved. Next, azathioprine was used for maintenance during the next 18 months.There were no disease flares during 24-month follow-up. CONCLUSION: Granulomatosis with polyangitis (Wegener's) with large organ involvement, affecting the central nervous system structures require a rapid diagnosis and intensive medication treatment in order to prevent or reduce irreversible damage. Our experience confirms the findings reported in the literature that the severe forms of the disease are associated with increased probability of achieving remission, which reflects increased responsiveness of such patients to immunosuppressant therapy.