Description

Simple

A medication used to treat osteoporosis in postmenopausal women at high risk of fracture.

Clinical

A parathyroid hormone-related protein (PTHrP) analog used for the treatment of osteoporosis in postmenopausal women with a high risk of fracture.

Overview

Abaloparatide is an analog of PTHrP (parathyroid hormone-related protein). It was approved in April 28, 2017 by the FDA (as Tymlos) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Abaloparatide is a synthetic peptide that is related to hPTHrP and has demonstrated in preclinical testing the potential to widen the anabolic window for bone therapeutics, stimulating bone formation with a limited effect on bone resorption and mineral mobilization. This could enable improved convenience over currently available anabolic therapies, resulting in greater compliance and, ultimately, greater benefit to patients.

Pharmacology

Indication

Investigated for use/treatment in postmenopausal osteoporosis to reduce vertebral and/or non-vertebral fractures.

Pharmacodynamic

Abaloparatide (BA058), a proprietary analog of human parathyroid hormone-related protein (hPTHrP), is currently undergoing clinical trials by the company for the treatment of osteoporosis in postmenopausal women. PTHrP is a critical peptide for promoting new bone formation, with a distinct role from... Read more

Mechanism of action

In target cells, abaloparatide acts as an agonist on PTH type 1 receptor (PTH1R) and activates both G protein–mediated cAMP signaling and β-arrestin-mediated ERK-1/2 signaling pathways with similar potency [A19105]. Abaloparatide binds to RG conformation of PTH1R with greater selectivity that result... Read more

Absorption

The time it takes to reach peak concentration following subcutaneous administration of 80 mcg abaloparatide ranges from 0.25 to 0.52 hr, with the median time of 0.51hr. The bioavailability in healthy women is 36% following administration.

Protein binding

In vitro plasma protein binding is approximately 70%.

Volume of distribution

Vd is approximately 50L.

Clearance

Information currently not available.

Half life

The mean (SD) half-life if 1.7 (0.7) hrs.

Route of elimination

Metabolized products are mainly eliminated via renal excretion. Patients with severe renal impairment should be monitored with increased risk of adverse effects however there are no recommended dosage adjustments in patients with mild, moderate or severe renal impairment.

Toxicity

Abaloparatide has shown to induce higher incidences of osteosarcoma in a dose-dependent manner in a 2 year carcinogenicity study with female and male rats. This correlation is not known to be reflected in humans, however patients with increased risk of osteosarcoma including Paget's disease, open e... Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type

Contraindications

Information currently not available.

Food Interactions

Information currently not available.