Calcitriol is the active form of vitamin D3 (cholecalciferol). The natural or endogenous supply of vitamin D in man mainly depends on ultraviolet light for conversion of 7-dehydrocholesterol to vitamin D3 in the skin. Vitamin D3 must be metabolically activated in the liver and the kidney before it is fully active on its target tissues. The initial transformation is catalyzed by a vitamin D3-25-hydroxylase enzyme present in the liver, and the product of this reaction is 25-(OH)D3 (calcifediol). The latter undergoes hydroxylation in the mitochondria of kidney tissue, and this reaction is activated by the renal 25-hydroxyvitamin D3-1-a-hydroxylase to produce 1,25-(OH)2D3 (calcitriol), the active form of vitamin D3.
1,25-Dihydroxycholecalciferol (calcitriol) and 1,25-dihydroxyergocalciferol appear to be metabolized to their respective trihydroxy metabolites (i.e., 1,24,25-trihydroxycholecalciferol, 1,24,25-trihydroxyergocalciferol) and to other compounds. The principal metabolite excreted in urine is calcitroic acid, which is more water soluble. Although all the metabolites of cholecalciferol and ergocalciferol have not been identified, hepatic microsomal enzymes may be involved in degrading metabolites of ergocalciferol and cholecalciferol.
Calcitriol /(1,25-dihydroxy-vitamin D)/ is hydroxylated to 1,24,25-(OH)3-D by a renal hydroxylase that is induced by calcitriol and suppressed by those factors that stimulate the 25-OHD-1-alpha-hydroxylase. This enzyme also hydroxylates 25-OHD to form 24,25-(OH)2D. Both 24-hydroxylated compounds are less active than calcitriol and presumably represent metabolites destined for excretion. Side chain oxidation of calcitriol also occurs.
To evaluate the relation between daily and fasting urinary calcium excretion and serum 1,25-dihydroxyvitamin D (II) concentrations, 6 healthy men were studied during control and during chronic oral calcitrol (I) administration (0.6, 1.2, or 1.8 nmols every 6 hours for 6-12 days) while they ate normal and low calcium diets (19.2 or 4.2 mmols Ca/day). Daily urinary calcium excretion was directly related to serum II concentrations, but increased more while subjects ate the normal calcium diet than when eating the low calcium diet. During I and ingestion of the low calcium diet, daily urinary calcium excretion averaged 7.32 mmole/day, exceeding the dietary calcium intake. Fasting urinary calcium/creatinine exceeded 0.34 mmol/mmol (the upper limit of normal) on either diet. When serum II concentrations are elevated, a high fasting urinary calcium/creatinine or high daily urinary calcium excretion, even on a low calcium diet, is insufficient criteria for the documentation of a renal calcium leak.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
皮质类固醇抵消维生素D类似物的作用。/维生素D类似物/
Corticosteroids counteract the effects of vitamin D analogs. /Vitamin D analogs/
Concurrent administration of thiazide diuretics and pharmacologic doses of vitamin D analogs in patients with hypoparathyroidism may result in hypercalcemia which may be transient and self-limited or may require discontinuance of vitamin D analogs. Thiazide-induced hypercalcemia in hypoparathyroid patients is probably caused by increased release of calcium from bone. /Vitamin D analogs/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
过度使用矿物油可能会干扰肠道对维生素D类似物的吸收。/维生素D类似物/
Excessive use of mineral oil may interfere with intestinal absorption of vitamin D analogs. /Vitamin D analogs/
Orlistat may result in decreased GI absorption of fat-soluble vitamins such as vitamin D analogs. At least 2 hours should elapse between (before or after) any orlistat dose and vitamin D analog administration ... . /Vitamin D analogs/
The treatment of acute accidental overdosage of Calcijex (calcitriol injection) should consist of general supportive measures. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion and assessment of electrocardiographic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and low calcium diet are also indicated in accidental overdosage. Due to the relatively short duration of the pharmacological action of calcitriol, further measures are probably unnecessary. Should, however, persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives which may be considered, depending on the patients' underlying condition. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce an appropriate forced diuresis. The use of peritoneal dialysis against a calcium-free dialysate has also been reported.
Many vitamin D analogs are readily absorbed from the GI tract following oral administration if fat absorption is normal. The presence of bile is required for absorption of ergocalciferol and the extent of GI absorption may be decreased in patients with hepatic, biliary, or GI disease (e.g., Crohn's disease, Whipple's disease, sprue). Because vitamin D is fat soluble, it is incorporated into chylomicrons and absorbed via the lymphatic system; approximately 80% of ingested vitamin D appears to be absorbed systemically through this mechanism, principally in the small intestine. Although some evidence suggested that intestinal absorption of vitamin D may be decreased in geriatric adults, other evidence did not show clinically important age-related alterations in GI absorption of the vitamin in therapeutic doses. It currently is not known whether aging alters the GI absorption of physiologic amounts of vitamin D. /Vitamin D analogs/
After oral administration of calcitriol, there is about a 2-hour lag-time before calcium absorption in the GI tract increases. Maximal hypercalcemic effect occurs in about 10 hours, and the duration of action of calcitriol is 3-5 days.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
达到峰值血清浓度的时间：口服：大约3到6小时。
Time to peak serum concentration: Oral: Approximately 3 to 6 hours.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
维生素D的主要排泄途径是胆汁；只有很小一部分摄入剂量会出现在尿液中。
The primary route of excretion of vitamin D is the bile; only a small percentage of an administered dose is found in urine. /Vitamin D/
