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.
◉ Summary of Use during Lactation:Calcitriol is the normal physiologically active form of vitamin D, 1,25-dihydroxyvitamin D. Several women with hyocalcemia have successfully breastfed during breastfeeding, with sometimes fluctuating serum calcium levels. Limited data indicate that its use in nursing mothers in appropriately adjusted doses does not affect the breastfed infant. If calcitriol is required by the mother, it is not a reason to discontinue breastfeeding. Calcitriol and calcium dosage requirements are usually reduced during lactation in women with hypoparathyroidism.
◉ Effects in Breastfed Infants:A woman with hypoparathyroidism breastfed her infant from week 1 to week 32 postpartum while taking calcitriol. The dose was initially 0.5 mcg daily, but was decreased to 0.25 mcg daily after 8 weeks. The infant thrived during breastfeeding and had normal serum calcium levels at 1 and 3 weeks and 3 months of age.
A woman breastfed infants after two pregnancies while taking calcitriol in doses of 0.75 and 1 mcg daily. There were no reports of adverse reactions.
A woman breastfed her newborn infant for 9 days while taking calcitriol 0.5 mcg three times daily. Calcitriol was stopped at that time because of hypercalcemia, but restarted at 40 days postpartum in low doses that were gradually increased until the prepregnancy dosage of 1.5 mcg daily was reached just before weaning at 12.5 months postpartum.
A woman with discoid lupus was taking calcitriol 0.25 mcg every 2 days and several other medications concurrently. Her infant was breastfed for 12 months and followed up at 15 months of age. No adverse effects were reported during breastfeeding and the infant was growing and developing normally at 15 months of age.
A nursing mother with autosomal dominant hypoparathyroidism type 1 was treated with teriparatide for 8 months postpartum then calcitriol 0.5 mcg twice daily was substituted. She breastfed her infant exclusively for 6 months then with supplementation to 1 year. Her infant had no change in serum calcium when maternal calcitriol was begun. The mother began weaning at 11 months and at 1 year of age weaning was complete. Growth and development were normal at 1.5 years of age.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)
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
过量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/
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/
Synthesis and biological activity of the 1α,25-dihydroxyvitamin D3 diastereomer with unnatural configuration at the rings C/D side-chain moiety
摘要：
1 alpha ,25-Dihydroxyvitamin D-3 diastereomer, differing from the parent compound in configuration at four asymmetric carbon atoms in the rings C/D and side chain (C13, C14, C17 and C20), was synthesized and shown to have a significant affinity for the vitamin D receptor. (C) 2000 Elsevier Science Ltd. All rights reserved.
1 alpha ,25-Dihydroxyvitamin D-3 diastereomer, differing from the parent compound in configuration at four asymmetric carbon atoms in the rings C/D and side chain (C13, C14, C17 and C20), was synthesized and shown to have a significant affinity for the vitamin D receptor. (C) 2000 Elsevier Science Ltd. All rights reserved.
