Vitamin D analogues
Ergocalciferol. The benefits of ergocalciferol (vitamin D2) include wide availability and low cost, but its unpredictability in an individual patient and long half-life make it less
than ideal.1-3,9 Initially, large doses (4,000 to 6,000 U/kg orally every 24 hours) are administered.1-3,10 Large doses may be required because of the lack of PTH effect, which normally aids in the conversion of ergocalciferol to
a more active analogue.1-3,9 Ergocalciferol is fat-soluble and distributes slowly throughout the body fat stores.1-3 An increase in serum calcium concentration may become apparent five to 21 days after initiation of therapy.1-3,10 Parenteral calcium supplementation can usually be discontinued one to five days after the start of ergocalciferol treatment.1,3 Once the serum calcium concentration is stable, the dose may be gradually decreased to between 1,000 and 2,000 U/kg once
daily to once weekly.1-3,10
Because the dose of ergocalciferol required by individual patients varies markedly, there is a risk for the development of
severe hypercalcemia.1,2 If a patient becomes hypercalcemic, the condition may persist for one to 18 weeks because of ergocalciferol's long half-life
and extensive fat distribution in the body.1,2 If hypercalcemia develops, treat it immediately by discontinuing ergocalciferol and calcium supplementation. If hypercalcemia
is refractory, consider administering intravenous fluid therapy with 0.9% sodium chloride solution, a noncalcium-retaining
diuretic such as furosemide, and corticosteroids.1 Corticosteroids increase calciuresis, reduce intestinal absorption of calcium, and inhibit calcium resorption.
Dihydrotachysterol. Dihydrotachysterol is a readily available synthetic vitamin D analogue that is superior to ergocalciferol because of its
potency, rapid onset of action, and half-life.1-3,10 For comparison, 1 mg of dihydrotachysterol is equivalent to 120,000 U of ergocalciferol.1,3 Also because of its molecular structure, dihydrotachysterol is not stored in fat to the same degree that ergocalciferol
is stored.1,2 In the liver, dihydrotachysterol undergoes 25-hydroxylation, forming a molecule similar to calcitriol; however, it is less
effective because it lacks a 3-beta-hydroxyl group.2,15 The onset of action of dihydrotachysterol is one to seven days, and it is eliminated from the system more rapidly after
discontinuation, usually in four to 14 days (although it may last 30 days),1-3,10 making it safer and easier to adjust the dose than ergocalciferol.3,10 However, dihydrotachysterol costs more than ergocalciferol. Some patients do not respond to the tablet or capsule formulations
of dihydrotachysterol but respond to a liquid formulation.1,3 Other animals are completely unresponsive to dihydrotachysterol and require therapy with calcitriol.1
The initial dosage of dihydrotachysterol is 0.03 mg/kg/day orally divided every 12 hours until an effect is demonstrated (usually
two to three days), then 0.02 mg/kg/day orally divided every 12 hours for two to three days, followed by a maintenance dosage
of 0.01 to 0.02 mg/kg/day orally divided every 12 hours and given every one to two days (one half is administered in the morning,
the other half in the evening; some patients require this every day, while others require it every other day).2,3 Although superior to ergocalciferol, there remains a substantial dose variation in the amount of dihydrotachysterol required
for individual patients.2
Calcitriol. Calcitriol (vitamin D3) is the ideal vitamin D analogue because of its potency and the precise control of serum calcium it allows.1,2,9,10 Calcitriol does not require activation and is not stored within the body.3,10 It has a rapid onset of action (one to four days) and a short half-life (less than a day), allowing for frequent dose adjustments.1-3,10 Because of this, there is minimal concern regarding induction of hypercalcemia if an animal is monitored as recommended.
If hypercalcemia develops, the calcitriol dose can be reduced or discontinued until the hypercalcemia resolves.1-3,10
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