L-甲状腺素钠盐五水合物

L-Thyroxine sodium (Levothyroxine sodium) 是一种合成的甲状腺激素,用于甲状腺功能减退症的研究。DIO 酶将 L-Thyroxine (T4) 转化成具有生物活性的三碘甲状腺氨酸 (T3)。

研究领域 >> 内分泌

信号通路 >> 其他 >> 甲状腺激素受体

脱碘酶(DIOs)催化甲状腺素(pro-hormone)转化为活跃的甲状腺激素,与促甲状腺激素(TSH)水平有关。DIO1和DIO2催化甲状腺激素分泌的激活,而DIO3则起到抑制分泌的作用。垂体分泌的负反馈和DIOS1的负反馈起关键作用。已知L-甲状腺素(T4)和三碘甲状腺素(T3)激素可调节离子通道、泵和调节收缩蛋白的表达。此外,甲状腺激素已被证明影响钙稳态和负责兴奋和收缩的流量,而L-甲状腺素和三碘甲状腺素调节其药理学控制和分泌。在喂食无碘饲料12周的大鼠中,与标准饲料喂养的对照组相比,三碘甲状腺素和L-甲状腺素水平显著降低(p<0.001)。在低剂量L-甲状腺素治疗组中,观察到L-甲状腺素水平增加(p=0.02),而三碘甲状腺素水平与对照组几乎相同(p=0.19)。与未经治疗的甲状腺功能减退组相比,大剂量L-甲状腺素治疗的大鼠的三碘甲状腺素和L-甲状腺素循环浓度均显著增加(分别为p<0.001和p=0.004),并且与对照值相比,L-甲状腺素水平显著增加(p=0.03)[2]。

[1]. Arici M, et al. Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients. Endocr J. 2018 Mar 28;65(3):317-323.

[2]. Corriveau S, et al. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animalmodel. J Clin Transl Endocrinol. 2015 Sep 9;2(4):144-149.

MOLECULAR FORMULA :

C15-H11-I4-N-O4.Na

MOLECULAR WEIGHT :

799.86

WISWESSER LINE NOTATION :

QR BI FI DOR BI FI D1YZVO &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

14 mg/kg/14D-I

TOXIC EFFECTS :

Behavioral - coma Cardiac - change in rate Gastrointestinal - hypermotility, diarrhea

REFERENCE :

AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 3,297,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

900 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Endocrine - evidence of thyroid hypofunction

REFERENCE :

AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 3,297,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

449 ug/kg

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP Vascular - BP elevation not characterized in autonomic section

REFERENCE :

AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 14,1114,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

117 ug/kg/60D-I

TOXIC EFFECTS :

Behavioral - headache

REFERENCE :

AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960- Volume(issue)/page/year: 138,927,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

20 ug/kg

TOXIC EFFECTS :

Behavioral - excitement Cardiac - pulse rate increase, without fall in BP Nutritional and Gross Metabolic - body temperature increase

REFERENCE :

AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960- Volume(issue)/page/year: 141,1025,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,905,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,905,1982 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

6750 ug/kg

SEX/DURATION :

female 10 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - other postnatal measures or effects

REFERENCE :

BNEOBV Biology of the Neonate. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.15- 1970- Volume(issue)/page/year: 31,71,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2 mg/kg

SEX/DURATION :

female 9-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

DPTHDL Developmental Pharmacology and Therapeutics. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 2,17,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

8 mg/kg

SEX/DURATION :

female 9-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

JDREAF Journal of Dental Research. (International Assoc. for Dental Research, 734 15th St., NW, Suite 809, Washington, DC 20005) V.1- 1919- Volume(issue)/page/year: 53(Spec Iss),541,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

30 ug/kg

SEX/DURATION :

female 28-30 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Effects on Newborn - stillbirth

REFERENCE :

BNEOBV Biology of the Neonate. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.15- 1970- Volume(issue)/page/year: 22,161,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 80525 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 2770 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 80525 No. of Facilities: 131 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 2447 (estimated) No. of Female Employees: 1413 (estimated)