Products
Calcitriol is commercially available in the form of capsules (e.g., Rocaltrol) and as an ointment for psoriasis (Silkis). The active ingredient has been approved in many countries since 1978. The oral solution has been off the market since 2012. The active ingredient content could not be ensured until the end of the shelf life. Capsules are a possible substitute for the solution. If the desired dose cannot be achieved with them, depending on the indication, a switch to the prodrug cholecalciferol, which is commercially available in the form of drops, is possible. In this case, a dose adjustment is necessary. However, a disadvantage of cholecalciferol is that metabolic conversion steps in the liver and kidney to calcitriol are necessary, which depend on organ function (see figure below). It is known that endogenous formation of calcitriol is reduced in renal diseases such as renal insufficiency and in hypoparathyroidism. Cholecalciferol is not approved for all calcitriol indications. Other options:
- Switch to alfacalcidol (1-hydroxycholecalciferol, Germany, drops), which is metabolized in the liver.
- Import of liquid dosage forms from abroad (USA).
- Production of magisterial formulations (difficulty: unstable substance, high cost).
Structure and properties
Calcitriol (C27H44O3, Mr = 416.6 g/mol) is a cholecalciferol hydroxylated in two positions. It is present in the form of white crystals that are practically insoluble in water. The substance is sensitive to air, heat and light.
Effects
Calcitriol (ATC A11CC04) is the active metabolite of cholecalciferol (= vitamin D3), which is formed in the body by a twofold hydroxylation at positions 1 and 25. Hydroxylation occurs first in the liver at position 25 and subsequently in the kidney at position 1. Vitamin D plays a critical role in the regulation of calcium and phosphate balance and promotes bone mineralization by increasing absorption in the intestine and reabsorption in the kidney.
Indications
- Postmenopausal osteoporosis
- Rickets
- Renal osteodystrophy in chronic renal failure.
- Hypoparathyroidism, pseudohypoparathyroidism.
- As an ointment: psoriasis
Adverse effects
Because of its higher potency, the risk of developing hypercalcemia is increased compared with cholecalciferol, and calcitriol may cause acute or chronic vitamin D toxicity.
