PTH (IC50 = 2 nM)[1]
Teriparatide selectively binds to and activates the parathyroid hormone 1 receptor (PTH1R), a class B G protein-coupled receptor expressed on osteoblasts and bone stromal cells. As a PTH1R agonist, teriparatide activates multiple signaling pathways including Gs/cAMP/PKA, Gq/PKC, and β-arrestin-mediated signaling, thereby promoting bone formation.

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.

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Teriparatide exerts its activity in vitro through activation of PTH1R. Studies using UMR-106 rat osteosarcoma cells have demonstrated that teriparatide (PTH1-34) binding to the receptor induces intracellular cAMP elevation, which can be quantitatively measured using time-resolved fluoroimmunoassay. Furthermore, the N-terminal region (amino acids 1-14) of PTH1-34 is critical for G protein signaling activation, while the C-terminal region (amino acids 23-34) primarily contributes to receptor binding.

Teriparatide (human parathyroid hormone-(1-34)) (20 μg/kg ih; once daily for 4 weeks; female New Zealand White rabbits) increases body weight and obesity [1].

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Intermittent administration of teriparatide (once-daily subcutaneous injection) significantly promotes bone formation, increases bone mineral density (BMD), and reduces fracture risk. Clinical studies in postmenopausal osteoporotic women have shown that teriparatide treatment for 48 weeks increases lumbar spine BMD by approximately 8% and femoral neck BMD by approximately 3-4%, with biosimilar products demonstrating comparable efficacy to the reference drug. The Fracture Prevention Trial demonstrated a 65% reduction in vertebral fracture risk and a 53% reduction in non-vertebral fracture risk after 18 months of treatment. Teriparatide also sustainably elevates serum P1NP (procollagen type 1 N-terminal propeptide) levels, reflecting enhanced bone formation. Importantly, continuous PTH exposure promotes bone resorption, making intermittent pulsatile administration critical for anabolic effects.

Radioligand binding assays are commonly used to evaluate the binding affinity of teriparatide to PTH1R in cell-free systems. Radiolabeled PTH analogues (e.g., ¹²⁵I-PTH(1-34)) are incubated with membrane preparations expressing PTH1R in the presence of increasing concentrations of unlabeled teriparatide. After incubation, bound and free radioligands are separated by filtration or centrifugation, and radioactivity is measured to calculate IC₅₀ or Kd values for binding affinity assessment.

A recently developed cell-based bioassay has been established to determine the biological activity of teriparatide. The procedure involves seeding UMR-106 rat osteosarcoma cells at 1,000 cells/well in 384-well plates, followed by treatment with serially diluted teriparatide reference standards or samples (starting concentration 4,000 ng/mL, 3-fold serial dilutions) in assay medium for 30 minutes at 25°C in the dark. After adding LANCE Ultra cAMP detection reagents and incubating for an additional 60 minutes at 25°C in the dark, intracellular cAMP levels are measured using time-resolved fluorescence resonance energy transfer, and relative potency is calculated using four-parameter fitting analysis.

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]

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Osteoporosis animal models, such as ovariectomized (OVX) mice or rats, are used to evaluate the in vivo activity of teriparatide. Animals receive daily subcutaneous injections of teriparatide (typically 20-40 µg/kg) for 4-8 weeks. Blood calcium levels and bone turnover markers are monitored periodically during the study. At study termination, bone tissue samples are collected for micro-computed tomography analysis to evaluate trabecular bone volume fraction, trabecular thickness, and other microstructural parameters. Histological staining is performed to assess osteoclast and osteoblast activity. In β-arrestin knockout mouse models, the bone-forming effect of teriparatide is attenuated, indicating involvement of the β-arrestin signaling pathway.

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 both hepatic and extrahepatic clearance. 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. Following a 20 μg subcutaneous dose, serum concentrations of the peptide peak within approximately 30 minutes and decline to undetectable levels within 3 hours. Biological Half-Life The serum half-life of teriparatide after intravenous injection is 5 minutes, and after subcutaneous injection, it is approximately 1 hour. A longer half-life after subcutaneous injection reflects the time required for the drug to be absorbed from the injection site.

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Teriparatide is rapidly absorbed into the systemic circulation following subcutaneous administration and has a short half-life, necessitating daily dosing to maintain therapeutic effects. In postmenopausal osteoporotic patients, a single 20 µg subcutaneous dose is rapidly eliminated. Clearance is reduced and elimination half-life prolonged in patients with renal impairment, while hepatic failure shows no significant effect. As a peptide hormone, teriparatide is primarily metabolized and cleared by the kidneys, with metabolites consisting of small peptides and amino acids without active accumulation. Biosimilar products demonstrate similar pharmacokinetic profiles to the reference drug.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
An infant with congenital hyperparathyroidism was breastfed while the mother was using teriparatide. Breastfeeding appeared to protect the infant from the effects of hypoparathyroidism. Signs and symptoms of hypercalcemia or hypocalcemia should be monitored in breastfed infants. Monitoring of serum calcium levels should be considered. Due to the potential risk of osteosarcoma identified in animal studies, the manufacturer recommends against breastfeeding during 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 mother continued calcitriol infusions at a dose of 27 to 30 micrograms daily, then reduced to 0.5 micrograms twice daily. The mother exclusively breastfed the infant for six months, followed by complementary feeding until one year of age. The infant's serum calcium levels did not change after the mother began calcitriol administration. The mother began weaning the infant at 11 months of age. After weaning, 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 collected after weaning showed a significant decrease in these levels. Breastfed infants appear to be protected from severe hypocalcemia by their mother's milk during the first year of life. Growth and development were normal at 1.5 years of age.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.

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Teriparatide is generally well-tolerated, with no clinical evidence of hepatotoxicity. Over a decade of clinical use, no cases of clinically apparent liver injury attributed to teriparatide have been reported (likelihood score: E) . Common adverse reactions include injection site reactions (pain, redness), nausea, vomiting, and headache. Hypercalcemia occurs in approximately 3-5% of patients and can typically be managed with adequate hydration. In animal studies, high-dose long-term administration was associated with an increased risk of osteosarcoma in rats, but this has not been confirmed in humans, with only a few suspected cases reported worldwide. Contraindications include a history of bone malignancy, unexplained elevated alkaline phosphatase levels, and use in children or pregnant women.

[1]. Influence of Teriparatide and Ibandronate on Cortical Bone in New Zealand White Rabbits: A HR-QCT Study. Calcif Tissue Int. 2016 Nov;99(5):535-542.

Teriparatide may be carcinogenic, depending on state or federal labeling requirements. Teriparatide is a polypeptide. This polypeptide consists of a 1-34 amino acid segment of human parathyroid hormone, specifically the biologically active N-terminal region. The acetate form is used for the differential diagnosis of hypoparathyroidism and pseudohypoparathyroidism and can be administered via intravenous infusion. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995) See also: Teriparatide (note moved to). Mechanism of Action: The effects of teriparatide on bone depend on the pattern of systemic exposure. Once-daily injections of teriparatide promote new bone formation on the surface of cancellous and cortical bone (periosteum and/or endosteum) by preferentially stimulating osteoblast activity rather than 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 manifest as increased bone mass, elevated markers of bone formation and resorption, and enhanced bone strength. Conversely, persistent excesses of endogenous parathyroid hormone (PTH) (such as in hyperparathyroidism) can be detrimental to bone because bone resorption may be stimulated more 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 phosphate, and intestinal calcium absorption. The biological effects of PTH and teriparatide are mediated by binding to specific high-affinity cell surface receptors. The 34 N-terminal amino acids of teriparatide and PTH bind to these receptors with the same affinity and produce the same physiological effects on bone and kidneys. Teriparatide is not expected to accumulate in bone or other tissues.

C181H291N55O51S2

4117.72

4116.134

C, 52.80; H, 7.12; N, 18.71; O, 19.82; S, 1.56

52232-67-4

Teriparatide acetate hydrate;99294-94-7

16133850

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;
H-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-OH;
L-seryl-L-valyl-L-seryl-L-alpha-glutamyl-L-isoleucyl-L-glutaminyl-L-leucyl-L-methionyl-L-histidyl-L-asparagyl-L-leucyl-glycyl-L-lysyl-L-histidyl-L-leucyl-L-asparagyl-L-seryl-L-methionyl-L-alpha-glutamyl-L-arginyl-L-valyl-L-alpha-glutamyl-L-tryptophyl-L-leucyl-L-arginyl-L-lysyl-L-lysyl-L-leucyl-L-glutaminyl-L-alpha-aspartyl-L-valyl-L-histidyl-L-asparagyl-L-phenylalanine

SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF

White to off-white solid powder

-18.7

60

62

146

289

9740

34

[SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF]

OGBMKVWORPGQRR-UMXFMPSGSA-N

InChI=1S/C181H291N55O51S2/c1-21-96(18)146(236-160(267)114(48-53-141(250)251)212-174(281)132(84-239)232-177(284)143(93(12)13)233-147(254)103(185)82-237)178(285)216-111(45-50-134(187)241)155(262)219-119(65-90(6)7)163(270)213-116(55-62-289-20)158(265)224-124(71-100-79-196-86-203-100)167(274)226-126(73-135(188)242)169(276)217-117(63-88(2)3)148(255)201-81-138(245)205-105(39-27-30-56-182)149(256)223-123(70-99-78-195-85-202-99)166(273)221-121(67-92(10)11)164(271)225-128(75-137(190)244)171(278)231-131(83-238)173(280)214-115(54-61-288-19)157(264)210-112(46-51-139(246)247)153(260)208-109(43-34-60-199-181(193)194)159(266)234-144(94(14)15)175(282)215-113(47-52-140(248)249)156(263)222-122(69-98-77-200-104-38-26-25-37-102(98)104)165(272)220-120(66-91(8)9)161(268)209-108(42-33-59-198-180(191)192)151(258)206-106(40-28-31-57-183)150(257)207-107(41-29-32-58-184)152(259)218-118(64-89(4)5)162(269)211-110(44-49-133(186)240)154(261)228-129(76-142(252)253)172(279)235-145(95(16)17)176(283)229-125(72-101-80-197-87-204-101)168(275)227-127(74-136(189)243)170(277)230-130(179(286)287)68-97-35-23-22-24-36-97/h22-26,35-38,77-80,85-96,103,105-132,143-146,200,237-239H,21,27-34,39-76,81-84,182-185H2,1-20H3,(H2,186,240)(H2,187,241)(H2,188,242)(H2,189,243)(H2,190,244)(H,195,202)(H,196,203)(H,197,204)(H,201,255)(H,205,245)(H,206,258)(H,207,257)(H,208,260)(H,209,268)(H,210,264)(H,211,269)(H,212,281)(H,213,270)(H,214,280)(H,215,282)(H,216,285)(H,217,276)(H,218,259)(H,219,262)(H,220,272)(H,221,273)(H,222,263)(H,223,256)(H,224,265)(H,225,271)(H,226,274)(H,227,275)(H,228,261)(H,229,283)(H,230,277)(H,231,278)(H,232,284)(H,233,254)(H,234,266)(H,235,279)(H,236,267)(H,246,247)(H,248,249)(H,250,251)(H,252,253)(H,286,287)(H4,191,192,198)(H4,193,194,199)/t96-,103-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,143-,144-,145-,146-/m0/s1

(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-oxopentanoic acid

PTH 1-34; HSDB7367; ZT 034; HSDB-7367; Parathar; Teriparatide acetate; 52232-67-4; Teriparatida; ZT034; ZT-034; HSDB 7367; Human parathyroid hormone 1-34; trade name Forteo

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

H2O : ~100 mg/mL (~24.3 mM)

Solubility in Formulation 1: 50 mg/mL (12.14 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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