25-Hydroxyvitamin D Pharmacokinetic Study

Pilot Clinical Trial to Evaluate the Pharmacokinetics of Orally Administered 25-hydroxyvitamin D3 and Vitamin D3 in Healthy Adults and Adults With a History of Intestinal Malabsorption

To evaluate the pharmacokinetic parameters of orally administered 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D3 from the corresponding serum concentration-time curves in healthy adults and adults with a history of intestinal malabsorption.

Patients with a history of intestinal malabsorption (n=10) and healthy volunteers (n=10); (of both sexes and all ethnicities) will be recruited in this randomized double-blind crossover study. All subjects will be prescreened for 25(OH)D levels to include subjects with 25(OH)D<30 ng/ml. The subjects will be randomized to receive a single oral dose of 900 µg of either vitamin D3 or 25(OH)D3. Blood samples will be taken at baseline and at 2,4,6,8,12 hours and days 1,2,3, 7 and 14. After a washout period of at least 14 days (2 weeks) the subjects will receive in a double blinded manner a single oral dose of 900 µg of either 25(OH)D3 or vitamin D3 (depending on which one they took in the randomization) any time after the washout. Blood samples will be taken at baseline and at 2,4,6,8,12 hours and days 1,2,3,7, 14.

Serum levels of calcium, phosphorus, albumin, creatinine, intact parathyroid hormone (iPTH) will be obtained at baseline and at day 14 (or within a reasonable time if unable to come in on the exact day). Vitamin D and 25(OH)D will be determined on all the blood samples collected at the various times.

Inclusion Criteria:

• Adult male or female with history of intestinal fat-malabsorption with confirmed diagnosis
• Taking vitamin D (ergocalciferol or cholecalciferol). Subjects taking vitamin D supplement of more than 2000 IUs (50 micrograms)/day) that may interfere with study endpoints must be willing and able to discontinue use of these supplements for the duration of the study and allow for at least a 14-day washout prior to prescreening and enrollment.
• Women of child bearing potential must be on birth control and not pregnant based on a negative pregnancy test at baseline for each of the 2 pharmacokinetic studies.
• Serum total 25(OH)D < 30 ng/mL

Exclusion Criteria:

• Unwilling to discontinue use of supplemental dose of vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) daily equivalent (2,000 IU/50 μg) 1 week or less prior to randomization and during the study
• On medications that can affect vitamin D metabolism including steroids such as prednisone, anti-seizure medications and medications to treat HIV.
• Tanning in a tanning bed at least one week before the study and throughout the duration of this study.
• Anyone anticipating going on holiday (where exposure to sun is imminent) 1 week before or during the entire study.
• Participation in the study or any reason which, in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely
• History of elevated serum calcium
• Chronic hepatic or renal failure
• Subjects with a history of an adverse reaction to orally administered vitamin D.
• Inability to give informed consent