骨化三醇

**骨化三醇**
临床数据
读音	美国 /ˌkælsɪˈtraɪɒl/; ; 英国 /kælˈsɪtriɒl/
商品名（英语：Drug nomenclature）	Rocaltrol, Calcijex, Decostriol, others
其他名称	1,25-dihydroxycholecalciferol, 1alpha,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3, 1α,25-(OH)2D3, 1,25(OH)2D
AHFS/Drugs.com	Monograph
MedlinePlus	a682335
核准状况	美 DailyMed: Calcitriol;
怀孕分级	澳: B3 ; ;
给药途径	口服给药, 静脉注射
ATC码	A11CC04 (WHO) D05AX03;
法律规范状态
法律规范	澳：限医生处方（S4）; 加：处方药（℞-only）; 英：处方药（℞-only） (POM); 美：处方药（℞-only）;
药物动力学数据
血浆蛋白结合率	99.9%
药物代谢	肾脏
生物半衰期	5–8小时 (成人), 27小时 (儿童)
排泄途径	粪便 (50%), 尿液 (16%)
识别信息
	IUPAC命名法 (1R,3S)-5-[2-[(1R,3aR,7aS)-1-[(2R)-6-hydroxy-6-methyl-heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H- inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol; ;
CAS号	32222-06-3
PubChem CID	5280453;
IUPHAR/BPS	2779;
DrugBank	DB00136 ;
ChemSpider	4444108 ;
UNII	FXC9231JVH;
KEGG	D00129;
ChEBI	CHEBI:17823 ;
ChEMBL	ChEMBL846 ;
PDB配体ID	VDX (PDBe, RCSB PDB);
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID5022722 ;
ECHA InfoCard	100.046.315
化学信息
化学式	C27H44O3
摩尔质量	416.65 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C;
	InChI InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1 ; Key:GMRQFYUYWCNGIN-NKMMMXOESA-N ;

骨化三醇（英语：Calcitriol，又称为1,25-二羟胆钙化醇或是1,25-二羟维生素D₃）是维生素D的活性形式，在正常的情况下由肾脏制造。它是一种激素，^[8]可结合并激活细胞核中的维生素D受体（英语：vitamin D receptor），而增加许多基因的表达。^[9]骨化三醇主要透过增加肠道对钙的吸收来增加血液中的钙质 (钙离子，Ca²⁺)。^[7]在调节血钙与血磷浓度方面有重要作用。

生物合成

7-脱氢胆固醇在皮肤内经紫外线的照射下生成胆钙化醇（维生素D₃），后者在肝脏中经羟化酶系的作用下羟化为25-羟胆钙化醇，继而经血液被转运到肾脏，肾脏近曲小管细胞中的CYP27B1（细胞色素 P450 27B1）将25-羟胆钙化醇羟化为1,25-二羟胆钙化醇。

当血液中维生素D、钙、磷的含量下降时，1,25-二羟胆钙化醇生成量会增加。甲状旁腺激素会增加肾脏中CYP27B1的活性，使得1,25-二羟胆钙化醇生成量增多，可协同甲状旁腺激素增加血钙。

生理作用

加速合成钙结合蛋白，而使得肠道吸收钙质。
促进肠道吸收磷。
同时增加破骨细胞与成骨细胞的数量，但对前者的效应要高于后者，故总体来说是增加血钙。
增强肾小管对钙和磷的重吸收，而减少尿液中钙的流失。

故总体来说，骨化三醇可增加血液中钙和磷的含量。

骨化三醇的作用原理很多情况下是通过与维生素D受体（VDR）结合，例如小肠上皮细胞细胞质中的受体与骨化三醇结合而成的配体-受体复合物转移到到细胞核中作为促进钙结合蛋白的编码基因的表达的转录因子，钙结合蛋白增加使细胞主动运输更多的钙离子，而提高钙离子吸收水平。吸收钙离子同时为维持电中性也需要运输阴离子，主要是吸收无机磷酸根离子，所以骨化三醇也可促进磷的吸收。^[10]

医疗应用

骨化三醇被用于治疗低血钙症、副肾上腺功能减退症（成人）、骨质软化，佝偻病（婴幼儿）、慢性肾脏病、肾性骨病、骨质疏松症，预防糖皮质素引起的骨质疏松症。^[11]骨化三醇和其他维生素D受体-配体类似物在调节血钙之外方面的应用也通过验证。^[12]其口服剂用于治疗干癣^[13]和干癣性关节炎。^[14]但对干癣的疗效证据尚不充分。^[15]维生素D类似物钙泊三醇是比较常用的治疗干癣药物。

副作用

骨化三醇可作为治疗肾病变引起的低血钙症和甲状旁腺功能亢进症、甲状旁腺功能昂进症引起的低血钙症、骨质疏松症、骨质软化症和家族性低磷血症（familial hypophosphatemia）。^[7]^[16]给药方式为透过口服或是静脉注射。^[7]过量使用会导致虚弱、头痛、恶心、便秘、泌尿道感染和腹痛等副作用。^[7]^[16]严重的副作用有高血钙和过敏性休克。^[7]建议个体在开始用药和改变剂量之后要定期进行血液检查。^[16]

相对于其他的维生素D化合物在临床上的使用（胆钙化醇，麦角钙化醇），骨化三醇有更高诱导高血钙症的风险。然而由于其相对短的生物半衰期，副作用也相对容易处理。^[11]

代谢

骨化三醇在体内的生物半衰期以小时为单位，而其前体骨化二醇的生物半衰期以周为单位。^[17]骨化三醇透过进一步羟基化形成1,24,25-三羟基维生素D、活性维生素 D3酸（英语：calcitroic acid）而失去活性。这是透过CYP24A1的作用而发生。^[18]活性维生素 D3酸更易溶于水，会随胆汁和尿液排出。

历史

骨化三醇于1971年首次由在美国教授Hector DeLuca（英语：Hector DeLuca）所主持实验室中工作的麦克·H.·郝力克（英语：Michael F. Holick），另外还有安东尼·诺曼（英语：Anthony W. Norman）及其同事们^[19]^[20]所发现。^[21]

骨化三醇于1971年被确定为维生素D的活性形式，于1978年在美国被批准用作医疗用途。^[7]它有通用名药物在市面贩售。^[16]它是美国于2021年排名第258最常使用的处方药，开立的处方笺数量超过100万张。^[22]^[23]

此药品已被列入世界卫生组织基本药物标准清单之中。^[24]

社会与文化

骨化三醇有多种商品名，如Rocaltrol (罗氏药厂)、Calcijex (亚培)、Decostriol (Mibe药厂、Jesalis药厂)、Vectical (Galderma药厂（英语：Galderma）) 和 Rolsical (太阳制药)。

参考资料

^ Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
^ Wolters Kluwer, Stedman's Medical Dictionary, Wolters Kluwer.
^ Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
^ Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, [2015-09-25], （原始内容存档于25 September 2015）.
^ Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster, [2015-09-25], （原始内容存档于2020-05-25）.
^ IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN): Nomenclature of vitamin D. Recommendations 1981. European Journal of Biochemistry. May 1982, 124 (2): 223–227. PMID 7094913. doi:10.1111/j.1432-1033.1982.tb06581.x .
^ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 Calcitriol Monograph for Professionals. Drugs.com. American Society of Health-System Pharmacists. [9 April 2019] （英语）.
^ "Nomenclature of Vitamin D. Recomendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN) （页面存档备份，存于互联网档案馆）" reproduced at the Queen Mary University of London website. Retrieved 21 March 2010.
^ Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. The American Journal of Clinical Nutrition. August 2008, 88 (2): 491S–499S. PMID 18689389. doi:10.1093/ajcn/88.2.491S .
^ Voet, Donald; Voet, Judith G. (2004). Biochemistry. Volume one. Biomolecules, mechanisms of enzyme action, and metabolism, 3rd edition, pp. 663–664. New York: John Wiley & Sons. ISBN 0-471-25090-2.
^ ^11.0 ^11.1 Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
^ Sunil Nagpal, Songqing Na, Radhakrishnan Rathnachalam. Noncalcemic actions of vitamin D receptor ligands. Endocrine Reviews. 2005-8, 26 (5): 662–687 [2019-02-12]. ISSN 0163-769X. doi:10.1210/er.2004-0002. （原始内容存档于2020-05-05）. 请检查|date=中的日期值 (帮助).
^ Smith, Ellen L.; Pincus, Stephanie H.; Donovan, Lynne; Holick, Michael F. A novel approach for the evaluation and treatment of psoriasis. Journal of the American Academy of Dermatology (Elsevier BV). 1988, 19 (3): 516–528. ISSN 0190-9622. doi:10.1016/s0190-9622(88)70207-8.
^ Huckins, David; Felson, David T.; Holick, Michael. Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: a pilot study. Arthritis & Rheumatism (Wiley-Blackwell). 1990, 33 (11): 1723–1727. ISSN 0004-3591. doi:10.1002/art.1780331117.
^ Calcitriol. In: Klasco RK, editor. Drugdex system. vol 128. Greenwood Village (CO): Thomson Micromedex; 2006.
^ ^16.0 ^16.1 ^16.2 ^16.3 British national formulary : BNF 76 76. Pharmaceutical Press. 2018: 1050–1051. ISBN 9780857113382.
^ Brandi ML. Indications on the use of vitamin D and vitamin D metabolites in clinical phenotypes. Clinical Cases in Mineral and Bone Metabolism. September 2010, 7 (3): 243–250. PMC 3213838 . PMID 22460535.
^ Jones G, Prosser DE, Kaufmann M. Cytochrome P450-mediated metabolism of vitamin D. Journal of Lipid Research. January 2014, 55 (1): 13–31. PMC 3927478 . PMID 23564710. doi:10.1194/jlr.R031534 .
^ Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ. Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry. July 1971, 10 (14): 2799–2804. PMID 4326883. doi:10.1021/bi00790a023.
^ Holick MF, Schnoes HK, DeLuca HF. Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proceedings of the National Academy of Sciences of the United States of America. April 1971, 68 (4): 803–804. Bibcode:1971PNAS...68..803H. PMC 389047 . PMID 4323790. doi:10.1073/pnas.68.4.803 .
^ Norman AW, Myrtle JF, Midgett RJ, Nowicki HG, Williams V, Popják G. 1,25-dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science. July 1971, 173 (3991): 51–54. Bibcode:1971Sci...173...51N. PMID 4325863. S2CID 35236666. doi:10.1126/science.173.3991.51.
^ The Top 300 of 2021. ClinCalc. [2024-01-14]. （原始内容存档于2024-01-15）.
^ Calcitriol - Drug Usage Statistics. ClinCalc. [2024-01-14].
^ World Health Organization. World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. hdl:10665/345533 . WHO/MHP/HPS/EML/2021.02.

Template:Vitamin D receptor modulators

[Dorlands-1] Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.

[Stedmans-2] Wolters Kluwer, Stedman's Medical Dictionary, Wolters Kluwer.

[MW_Medical-3] Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.

[AHD-4] Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, [2015-09-25], （原始内容存档于25 September 2015）.

[MWU-5] Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster, [2015-09-25], （原始内容存档于2020-05-25）.

[Nomen1981-6] IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN): Nomenclature of vitamin D. Recommendations 1981. European Journal of Biochemistry. May 1982, 124 (2): 223–227. PMID 7094913. doi:10.1111/j.1432-1033.1982.tb06581.x .

[AHFS2019-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 ^7.6 Calcitriol Monograph for Professionals. Drugs.com. American Society of Health-System Pharmacists. [9 April 2019] （英语）.

[8] "Nomenclature of Vitamin D. Recomendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN) （页面存档备份，存于互联网档案馆）" reproduced at the Queen Mary University of London website. Retrieved 21 March 2010.

[Norman_2008-9] Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. The American Journal of Clinical Nutrition. August 2008, 88 (2): 491S–499S. PMID 18689389. doi:10.1093/ajcn/88.2.491S .

[Voet-10] Voet, Donald; Voet, Judith G. (2004). Biochemistry. Volume one. Biomolecules, mechanisms of enzyme action, and metabolism, 3rd edition, pp. 663–664. New York: John Wiley & Sons. ISBN 0-471-25090-2.

[AMH2006-11] 11.0 ^11.1 Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3

[12] Sunil Nagpal, Songqing Na, Radhakrishnan Rathnachalam. Noncalcemic actions of vitamin D receptor ligands. Endocrine Reviews. 2005-8, 26 (5): 662–687 [2019-02-12]. ISSN 0163-769X. doi:10.1210/er.2004-0002. （原始内容存档于2020-05-05）. 请检查|date=中的日期值 (帮助).

[13] Smith, Ellen L.; Pincus, Stephanie H.; Donovan, Lynne; Holick, Michael F. A novel approach for the evaluation and treatment of psoriasis. Journal of the American Academy of Dermatology (Elsevier BV). 1988, 19 (3): 516–528. ISSN 0190-9622. doi:10.1016/s0190-9622(88)70207-8.

[14] Huckins, David; Felson, David T.; Holick, Michael. Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: a pilot study. Arthritis & Rheumatism (Wiley-Blackwell). 1990, 33 (11): 1723–1727. ISSN 0004-3591. doi:10.1002/art.1780331117.

[MicromedexDrugdex-15] Calcitriol. In: Klasco RK, editor. Drugdex system. vol 128. Greenwood Village (CO): Thomson Micromedex; 2006.

[BNF76-16] 16.0 ^16.1 ^16.2 ^16.3 British national formulary : BNF 76 76. Pharmaceutical Press. 2018: 1050–1051. ISBN 9780857113382.

[17] Brandi ML. Indications on the use of vitamin D and vitamin D metabolites in clinical phenotypes. Clinical Cases in Mineral and Bone Metabolism. September 2010, 7 (3): 243–250. PMC 3213838 . PMID 22460535.

[18] Jones G, Prosser DE, Kaufmann M. Cytochrome P450-mediated metabolism of vitamin D. Journal of Lipid Research. January 2014, 55 (1): 13–31. PMC 3927478 . PMID 23564710. doi:10.1194/jlr.R031534 .

[19] Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ. Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry. July 1971, 10 (14): 2799–2804. PMID 4326883. doi:10.1021/bi00790a023.

[pmid4323790-20] Holick MF, Schnoes HK, DeLuca HF. Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proceedings of the National Academy of Sciences of the United States of America. April 1971, 68 (4): 803–804. Bibcode:1971PNAS...68..803H. PMC 389047 . PMID 4323790. doi:10.1073/pnas.68.4.803 .

[pmid4325863-21] Norman AW, Myrtle JF, Midgett RJ, Nowicki HG, Williams V, Popják G. 1,25-dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science. July 1971, 173 (3991): 51–54. Bibcode:1971Sci...173...51N. PMID 4325863. S2CID 35236666. doi:10.1126/science.173.3991.51.

[22] The Top 300 of 2021. ClinCalc. [2024-01-14]. （原始内容存档于2024-01-15）.

[23] Calcitriol - Drug Usage Statistics. ClinCalc. [2024-01-14].

[WHO22nd-24] World Health Organization. World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. hdl:10665/345533 . WHO/MHP/HPS/EML/2021.02.

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