Pharmacokinetics and Pharmacodynamics of Subcutaneous Recombinant Parathyroid Hormone (1–84) in Patients With Hypoparathyroidism: An Open-Label, Single-Dose, Phase I Study

Clarke, B.L.; Berg, Jolene Kay; Fox, John; Cyran, J; Lagast, Hjalmar

doi:10.1016/j.clinthera.2014.04.001

Cited by 46 publications

(45 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ПТГ(1-84) выпускается в форме шприц-ручки и используется в режи-ме однократных подкожных инъекций в дозах 25, 50, 75 или 100 мкг. Период полувыведения ПТГ(1-84) больше, чем у ПТГ(1-34), что объ-ясняет возможность назначения препарата 1 раз в сутки [47][48][49].…”

Section: рекомбинантный человеческий птг(1-84)unclassified

Hypoparathyroidism: disease update and new methods of treatment

et al. 2017

View full text Add to dashboard Cite

Ключевые слова : гипопаратиреоз, гипокальциемия, паратиреоидный гормон, гиперфосфатемия, терипаратид, рекомбинантный человеческий паратиреоидный гормон 1-84. Hypoparathyroidism is characterized by hypocalcaemia and normal or low levels of parathyroid hormone (PTH). The most common cause of hypoparathyroidism is damage to the parathyroid glands during anterior neck surgery. Conventional management of hypoparathyroidism is focused upon maintaining the serum calcium with oral calcium and active vitamin D, often requiring high doses and giving rise to concerns about long-term consequences including extracellular calcification and kidney stones. With current treatment, patients may suffer from large swings in serum calcium and are at a substantial risk of chronic renal failure, extracellular calcification. Replacement therapy of recombinant human PTH(1-84) can open up new opportunities for better control and improvement of quality of life.

show abstract

Section: рекомбинантный человеческий птг(1-84)unclassified

Hypoparathyroidism: disease update and new methods of treatment

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Наиболее перспективными в настоящее время представляются работы в области трансплантационных методик и заместительной терапии паратиреоидным гормоном [1,2]. Одна из сложностей в оценке эффективности этиотропного лечения -от-сутствие стандартизированной общепринятой модели гипопаратиреоза.…”

Section: актуальные вопросы патофизиологии обоснованиеunclassified

“…У всех крыс обнаружено достоверное снижение со-держания ионизированного кальция и паратиреоидного гормона по сравнению с нормальным значением [1,22 (1,21; 1,25) ммоль/л и 30,5 (30; 32) пг/мл, соответствен-но; p U ≤0,05], однако обращает на себя внимание, что в группе 2 уровень гипокальциемии был более однороден (отличие между максимальным и минимальным по-казателем кальция составило 0,12 ммоль/л, тогда как в группе 1 -0,3 ммоль/л).…”

Section: основные результаты исследованияunclassified

Parathyreoidectomy in Rats Using Microsurgery and Medical Adhesive Sulfacrylate

Av¹,

Лепехова

et al. 2015

ARAMS

View full text Add to dashboard Cite

“…A full-length form of recombinant human PTH (1-84; Natpara) is approved for management of HP, requiring daily injections (Bilezikian et al, 2011;Mannstadt et al, 2013;Clarke et al, 2014). The shorter PTH (1-34) has been evaluated in studies of patients with transient postsurgical HP (Shah et al, 2015) and congenital forms of the disease (Winer et al, 2003;Theman et al, 2009;Gafni et al, 2012;Winer et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Repurposing a novel parathyroid hormone analogue to treat hypoparathyroidism

Krishnan

Chen

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEHuman parathyroid hormone (PTH) is critical for maintaining physiological calcium homeostasis and plays an important role in the formation and maintenance of the bone. Full-length PTH and a truncated peptide form are approved for treatment of hypoparathyroidism and osteoporosis respectively. Our initial goal was to develop an improved PTH therapy for osteoporosis, but clinical development was halted. The novel compound was then repurposed as an improved therapy for hypoparathyroidism. EXPERIMENTAL APPROACHA longer-acting form of PTH was synthesised by altering the peptide to increase cell surface residence time of the bound ligand to its receptor. In vitro screening identified a compound, which was tested in an animal model of osteoporosis before entering human trials. This compound was subsequently tested in two independent animal models of hypoparathyroidism. KEY RESULTSThe peptide identified, LY627-2K, exhibited delayed internalization kinetics. In an ovariectomy-induced bone loss rat model, LY627-2K demonstrated improved vertebral bone mineral density and biomechanical properties at skeletal sites and a modest increase in serum calcium. In a Phase I clinical study, dose-dependent increases in serum calcium were reproduced. These observations prompted us to explore a second indication, hypoparathyroidism. In animal models of this disease, LY627-2K restored serum calcium, comparing favourably to treatment with wild-type PTH. CONCLUSIONS AND IMPLICATIONSWe summarize the repositioning of a therapeutic candidate with substantial preclinical and clinical data. Our results support its repurposing and continued development, from a common indication (osteoporosis) to a rare disease (hypoparathyroidism) by exploiting a shared molecular target.

show abstract

Pharmacokinetics and Pharmacodynamics of Subcutaneous Recombinant Parathyroid Hormone (1–84) in Patients With Hypoparathyroidism: An Open-Label, Single-Dose, Phase I Study

Abstract: PTH replacement therapy with rhPTH(1-84) regulated mineral homeostasis of calcium, magnesium, phosphate, and vitamin D metabolism toward normal in these study patients with hypoparathyroidism.

Cited by 46 publications

References 18 publications

Hypoparathyroidism: disease update and new methods of treatment

Hypoparathyroidism: disease update and new methods of treatment

Parathyreoidectomy in Rats Using Microsurgery and Medical Adhesive Sulfacrylate

Repurposing a novel parathyroid hormone analogue to treat hypoparathyroidism

Contact Info

Product

Resources

About