PTH (IC50 = 2 nM)[1]

Teriparatide is a polypeptide that acts as a PTH1 receptor agonist. It can also cause cancer according to state or federal government labeling requirements. It is a polypeptide that consists of the 1-34 amino-acid fragment of human PARATHYROID HORMONE, the biologically active N-terminal region. The acetate form is given by intravenous infusion in the differential diagnosis of HYPOPARATHYROIDISM and PSEUDOHYPOPARATHYROIDISM.

Teriparatide acetate hydrate, also known as human parathyroid hormone-(1-34) acetate hydrate, enhances cortical thickness and porosity in female New Zealand white rabbits (20 μg/kg IV; once daily for 4 weeks)[1].

Animal/Disease Models: Female New Zealand White Rabbit[1]
Doses: 20 μg/kg
Route of Administration: subcutaneous injection; one time/day for 4 weeks
Experimental Results: Increased porosity, number and density as well as cortical area, thickness and bone mineral content ( BMC), but had no significant effect on volumetric bone mineral density (BMD).

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Forty-two female New Zealand white rabbits (17–21 weeks old) were housed in an animal room (temperature, 19 °C; humidity, 50 %; and a 12-h on/off light cycle) with free access to water. Rabbits were fed a chow diet (RC-4, 120 g/day). After 10 days of adaptation to their new environment, the rabbits (18–22 weeks old) were randomized into six groups of 7 animals each using the stratified weight method, as follows: 4-week vehicle administration group (4W-Veh), 4-week Teriparatide (TPTD) administration group (4W-TPTD: 20 μg/kg, subcutaneously [s.c.], daily), 12-week vehicle administration group (12W-Veh), 4-week TPTD administration + 8-week vehicle administration group (4W-TPTD + 8W-Veh), 4-week TPTD administration + 8-week lower-dose IBN administration group (4W-TPTD + 8W-IBN(L): 20 μg/kg of IBN, s.c., every 4 weeks), and 4-week TPTD administration + 8-week higher-dose IBN administration group (4W-TPTD + 8W-IBN(H): 100 μg/kg of IBN, s.c., every 4 weeks). The TPTD (human recombinant teriparatide) dose was selected based on the results of a previous rabbit study. The IBN doses were determined based on the results of previous ovariectomized monkey studies. Body weight was monitored weekly.[1]

Absorption, Distribution, and Excretion
Teriparatide's systemic clearance (approximately 62 L/hr for women and 94 L/hr for men) exceeds normal hepatic plasma flow, consistent with hepatic and extrahepatic clearance pathways. Following intravenous injection, the volume of distribution is approximately 0.12 L/kg. Inter-individual variability in systemic clearance and volume of distribution ranges from 25% to 50%.
Following subcutaneous injection, teriparatide is extensively absorbed; based on pooled data from the 20 μg, 40 μg, and 80 μg dose groups, its absolute bioavailability is approximately 95%. Both absorption and elimination rates are rapid. Peak serum concentrations of the peptide are reached approximately 30 minutes after subcutaneous injection of a 20 μg dose and decrease to unquantifiable concentrations within 3 hours.
Biological Half-Life
The half-life of teriparatide in serum is 5 minutes after intravenous injection and approximately 1 hour after subcutaneous injection. The longer half-life after subcutaneous injection reflects the time required for drug absorption from the injection site.

Effects during pregnancy and lactation
◉ Overview of medication use during lactation
An infant with congenital hyperparathyroidism was breastfed while the mother was using teriparatide. Breastfeeding appeared to protect the infant from hypoparathyroidism. Serum calcium levels in breastfed infants should be monitored regularly while the mother is receiving teriparatide treatment.
◉ Effects on breastfed infants
A woman with autosomal dominant hypoparathyroidism type 1 (ADH1) received teriparatide treatment during pregnancy at 28 mcg daily via continuous intravenous infusion. She also took 1000 IU of vitamin D3 daily, 400 mg of magnesium oxide twice daily, and 0 to 3 g of calcium carbonate orally based on serum calcium levels. Eight months postpartum, the infusion continued at 27 to 30 mcg daily, and calcitriol was switched to twice daily at 0.5 mcg. She exclusively breastfed her infant for 6 months, then introduced complementary foods until 1 year of age. When the mother started taking calcitriol, the infant's serum calcium levels did not change. The mother began weaning the infant at 11 months of age, and after weaning was completed at 1 year of age, the infant developed hypocalcemia and was diagnosed with ADH1, sharing the same gene mutation as the mother and other family members. During the first year of lactation, the infant's serum parathyroid hormone-related protein levels were within the median of the normal range. A sample taken after weaning showed a significant decrease in these levels. Breastfed infants appear to be protected from severe hypocalcemia during the first year of life by breast milk. At 1.5 years of age, the infant's growth and development were normal.
◉ Effects on breastfeeding and breast milk
As of the revision date, no relevant published information was found.

[1]. Iwamoto J, et, al. Influence of Teriparatide and Ibandronate on Cortical Bone in New Zealand White Rabbits: A HR-QCT Study. Calcif Tissue Int. 2016

Teriparatide (TPTD) is known to increase cortical bone thickness and porosity. This study aimed to investigate whether replacing TPTD with ibandronate (IBN) in an adult rabbit model could improve cortical bone parameters, which were evaluated using high-resolution quantitative computed tomography (HR-QCT). Forty-two female New Zealand white rabbits (18-22 weeks old) were randomly divided into six groups of seven each: a 4-week vector control group, a 4-week TPTD administration group (20 μg/kg, subcutaneous injection, once daily), a 12-week vector control group, a 4-week TPTD administration group + an 8-week vector control group, a 4-week TPTD administration group + an 8-week low-dose IBN administration group (20 μg/kg, subcutaneous injection, every 4 weeks), and a 4-week TPTD administration group + an 8-week high-dose IBN administration group (100 μg/kg, subcutaneous injection, every 4 weeks). After the 4-week or 12-week experiment, cortical bone from the distal femur was harvested for high-resolution quantitative CT (HR-QCT) analysis. Four weeks of TPTD administration increased bone porosity, number, and density, as well as cortical area, thickness, and bone mineral content (BMC), but had no significant effect on volumetric bone mineral density (BMD). Compared to four weeks of TPTD administration, four weeks of TPTD administration followed by eight weeks of excipient administration decreased bone porosity, number, and density, as well as cortical area and thickness, but its bone porosity, cortical area, and thickness were still higher than those of 12 weeks of excipient administration. Compared to four weeks of TPTD administration followed by eight weeks of excipient administration, four weeks of TPTD administration followed by eight weeks of high-dose IBN administration (rather than four weeks of TPTD administration followed by eight weeks of low-dose IBN administration) increased cortical area, thickness, BMC, and volumetric BMD, and decreased bone porosity, but did not decrease bone porosity or density. These results indicate that administration of higher doses of IBN after TPTD treatment is beneficial for bone mineral content (BMC), volumetric bone mineral density (BMD), cortical area, thickness, and porosity in adult rabbits. [1]

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Therapeutic Use: Bone Mineral Degradation Protectant
Forteo is indicated for the treatment of postmenopausal women with osteoporosis at high risk of fracture. These women include those with a history of osteoporotic fractures, multiple fracture risk factors, or those who have failed or are intolerant of previous osteoporosis treatments, subject to physician evaluation. In postmenopausal women with osteoporosis, Forteo can increase bone mineral density and reduce the risk of vertebral and nonvertebral fractures.
Forteo is also indicated for increasing bone mass in men with primary or hypogonadal osteoporosis at high risk of fracture. These men include those with a history of osteoporotic fractures, multiple fracture risk factors, or those who have failed or are intolerant of previous osteoporosis treatments, as assessed by a physician. For men with primary or hypogonadal osteoporosis, Forteo can increase bone mineral density. The effect of Forteo on fracture risk in men has not been studied.

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Drug Warning: In male and female rats, teriparatide increases the incidence of osteosarcoma (a malignant bone tumor), and the degree of increase is related to dose and duration of treatment. This effect was observed at systemic exposures to teriparatide at doses 3 to 60 times higher than the human exposure to a 20 μg dose. Because the relevance of the rat osteosarcoma finding to humans is uncertain, teriparatide should only be prescribed to patients for whom the potential benefit outweighs the potential risk.

Teriparatide should not be prescribed to patients at increased baseline risk for osteosarcoma (including those with Paget's disease or unexplained elevation of alkaline phosphatase, unclosed epiphyses, or a history of external beam radiation therapy or implant-based radiation therapy involving the bone).
Adverse reactions reported as an increase in teriparatide treatment in clinical trials include leg cramps and dizziness. Adverse reactions reported in at least 2% of patients receiving teriparatide, at a higher incidence than in the placebo group, but without established causality, include pain, arthralgia, rhinitis, fatigue, nausea, dizziness, headache, hypertension, exacerbated cough, pharyngitis, constipation, indigestion, diarrhea, rash, insomnia, depression, pneumonia, vertigo, dyspnea, neck pain, vomiting, syncope, leg cramps, angina, gastrointestinal disorders, sweating, or dental problems.
Transient episodes of symptomatic orthostatic hypotension have been occasionally observed in short-term clinical pharmacology studies of teriparatide. Typically, such events occur within 4 hours of administration and resolve spontaneously within minutes to hours. Transient orthostatic hypotension usually occurs after the first few doses and is relieved by the patient adopting a reclining position, without affecting continued treatment. The safety and efficacy of Forteo have not been evaluated in treatment exceeding 2 years. Therefore, use of this drug for more than 2 years is not recommended. In clinical trials, the incidence of urinary tract stones was similar in the Forteo treatment group and the placebo group. However, Forteo has not been studied in patients with active urinary tract stones. If active urinary tract stones or a history of hypercalciuria are suspected, urinary calcium excretion should be measured. Because Forteo may exacerbate active or recent urinary tract stones, it should be used with caution in patients with active or recent urinary tract stones. Physician's Desk Reference, 60th edition, Thomson PDR, Montvale, NJ, 2006, p. 119. 1741

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Mechanism of action: The effects of teriparatide on bone depend on its systemic exposure pattern. Teriparatide, administered once daily, promotes new bone formation on the surface of cancellous and cortical bone (periosteum and/or endosteum) by preferentially stimulating osteoblast activity over osteoclast activity. In monkey studies, teriparatide improved trabecular microstructure and increased bone mass and strength by stimulating new bone formation in cancellous and cortical bone. In humans, the anabolic effects of teriparatide are manifested as increased bone mass, elevated markers of bone formation and resorption, and enhanced bone strength. Conversely, persistent excess of endogenous parathyroid hormone (PTH) (such as in hyperparathyroidism) may be detrimental to bone health because bone resorption may be more stimulated than bone formation. Endogenous parathyroid hormone (PTH), composed of 84 amino acids, is a major regulator of calcium and phosphorus metabolism in bone and kidneys. The physiological functions of PTH include regulating bone metabolism, renal tubular reabsorption of calcium and phosphorus, and intestinal calcium absorption. The biological effects of PTH and teriparatide are mediated by binding to specific high-affinity cell surface receptors. Teriparatide and PTH bind to these receptors with the same affinity for their 34 N-terminal amino acids and have the same physiological effects on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.

C181H291N55O51S2.C2H4O2

4177.76709999997

C, 52.61; H, 7.12; N, 18.44; O, 20.30; S, 1.53

99294-94-7

Teriparatide;52232-67-4

Ser-Val-Ser-Glu-Ile-Gln-Leu-Met-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser-Met-Glu-Arg-Val-Glu-Trp-Leu-Arg-Lys-Lys-Leu-Gln-Asp-Val-His-Asn-Phe

SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF

Typically exists as solid at room temperature

H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2, acetate

Parathar acetate hPTH 1-34Teriparatide acetate Forteo

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)