An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation.
Bone
; 46(2): 534-42, 2010 Feb.
Article
en En
| MEDLINE
| ID: mdl-19786130
ABSTRACT
Daily subcutaneous administration of exogenous parathyroid hormone (PTH) promotes bone formation in patients with osteoporosis. Here we describe two novel, short-acting calcium-sensing receptor antagonists (SB-423562 and its orally bioavailable precursor, SB-423557) that elicit transient PTH release from the parathyroid gland in several preclinical species and in humans. In an ovariectomized rat model of bone loss, daily oral administration of SB-423557 promoted bone formation and improved parameters of bone strength at lumbar spine, proximal tibia and midshaft femur. Chronic administration of SB-423557 did not increase parathyroid cell proliferation in rats. In healthy human volunteers, single doses of intravenous SB-423562 and oral SB-423557 elicited transient elevations of endogenous PTH concentrations in a profile similar to that observed with subcutaneously administered PTH. Both agents were well tolerated in humans. Transient increases in serum calcium, an expected effect of increased parathyroid hormone concentrations, were observed post-dose at the higher doses of SB-423557 studied. These data constitute an early proof of principle in humans and provide the basis for further development of this class of compound as a novel, orally administered bone-forming treatment for osteoporosis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Hormona Paratiroidea
/
Fenilpropionatos
/
Receptores Sensibles al Calcio
/
Etanolaminas
/
Naftalenos
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bone
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos