Pharmacokinetic Comparison of Vitamins D2 and D3 in Stage 5 Chronic Kidney Disease Patients on Chronic Hemodialysis
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Date
2013-06-11Author
Schechinger, Erin
Laughlin, Ann M.
Armas, Laura A. G.
Lappe, Joan M.
Schwartz, Misty
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ABSTRACT
Background and Objectives: Recent understanding of extrarenal production of calcitriol has lead to the exploration of calciferol treatment in dialysis patients. This paper reports the pharmacokinetics of 25-hydroxyvitamin D (25(OH)D) response to a single, 50,000 IU dose of cholecalciferol, ergocalciferol, or placebo in subjects on chronic hemodialysis. Design, setting, participants, & measurements: This randomized, single blind, placebo controlled trial of calciferol in subjects with stage 5 chronic kidney disease requiring hemodialysis was conducted from November 2012 to March of 2013. The results for 26 subjects were analyzed and the time course of serum 25(OH)D was measured at days 0, 2,4,7,21, and 28 for intervention groups and days 0 and 28 for placebo. Additionally, blood was drawn at each time point calcium, phosphorus, and albumin. Results: The median baseline 25(OH)D level was 18.3 ng/ ml in the Vitamin D2 group and 15.9 ng/ ml in the D3 group, a nonsignificant difference. There was a significant increase in 25(OH)D levels in both the Vitamin D2 and D3 groups and a statistically significant decline in the 25(OH)D levels in the placebo controlled group. The mean Cmax rise from baseline (mean ±standard deviation) was 7 ± 2.04 ng/ml in the D2 group and 8.66± 2.96 ng/ml in the D3 group. The peak occurred at (median Tmax) day 7 for D2 and day 14 for D3, and the serum concentration maintained thereafter. In our study, the median Area Under the Curve (AUC) for day 28 for vitamin D2 was 183.025 ngd/ml, whereas the median AUC28 for vitamin was 163.3 ngd/ml. There was no significance difference between the AUC28 for the two groups (p=.368) at the 28 day data analysis. There was a statistically significant decline in calcium levels for the Vitamin D2 group but no other statistically significant changes in levels of albumin, phosphorus, or calcium in any other group. Conclusions: To our knowledge, this is the first study quantifying the 25(OH)D dose response and pharmacokinetics of oral cholecalciferol and ergocalciferol in subjects on chronic hemodialysis. Supplementation with calciferol to increase levels of 25(OH)D appears to be an important therapeutic management technique for patients in stage 5 Chronic Kidney Disease. In the 28 days that participants were studied, there were significant increases in 25(OH)D levels for both intervention groups. There appears to be no significant difference in the rise between the vitamin D2 and vitamin D3 groups, implying that either form of vitamin D can be used in this population. Our study highlighted that repletion of 25(OH)D levels with the use calciferol is a safe, efficient, and cost effective strategy to increase concentrations in hemodialysis patients.
Background and Objectives: Recent understanding of extrarenal production of calcitriol has lead to the exploration of calciferol treatment in dialysis patients. This paper reports the pharmacokinetics of 25-hydroxyvitamin D (25(OH)D) response to a single, 50,000 IU dose of cholecalciferol, ergocalciferol, or placebo in subjects on chronic hemodialysis. Design, setting, participants, & measurements: This randomized, single blind, placebo controlled trial of calciferol in subjects with stage 5 chronic kidney disease requiring hemodialysis was conducted from November 2012 to March of 2013. The results for 26 subjects were analyzed and the time course of serum 25(OH)D was measured at days 0, 2,4,7,21, and 28 for intervention groups and days 0 and 28 for placebo. Additionally, blood was drawn at each time point calcium, phosphorus, and albumin. Results: The median baseline 25(OH)D level was 18.3 ng/ ml in the Vitamin D2 group and 15.9 ng/ ml in the D3 group, a nonsignificant difference. There was a significant increase in 25(OH)D levels in both the Vitamin D2 and D3 groups and a statistically significant decline in the 25(OH)D levels in the placebo controlled group. The mean Cmax rise from baseline (mean ±standard deviation) was 7 ± 2.04 ng/ml in the D2 group and 8.66± 2.96 ng/ml in the D3 group. The peak occurred at (median Tmax) day 7 for D2 and day 14 for D3, and the serum concentration maintained thereafter. In our study, the median Area Under the Curve (AUC) for day 28 for vitamin D2 was 183.025 ngd/ml, whereas the median AUC28 for vitamin was 163.3 ngd/ml. There was no significance difference between the AUC28 for the two groups (p=.368) at the 28 day data analysis. There was a statistically significant decline in calcium levels for the Vitamin D2 group but no other statistically significant changes in levels of albumin, phosphorus, or calcium in any other group. Conclusions: To our knowledge, this is the first study quantifying the 25(OH)D dose response and pharmacokinetics of oral cholecalciferol and ergocalciferol in subjects on chronic hemodialysis. Supplementation with calciferol to increase levels of 25(OH)D appears to be an important therapeutic management technique for patients in stage 5 Chronic Kidney Disease. In the 28 days that participants were studied, there were significant increases in 25(OH)D levels for both intervention groups. There appears to be no significant difference in the rise between the vitamin D2 and vitamin D3 groups, implying that either form of vitamin D can be used in this population. Our study highlighted that repletion of 25(OH)D levels with the use calciferol is a safe, efficient, and cost effective strategy to increase concentrations in hemodialysis patients.