Teriparatide Forteo

Structural Formula Ball-and-Stick Model Space-filling Model

0 = Carbon = Hydrogen ^ = Oxygen ^ = Nitrogen ^ = Sulfur

Year of discovery: 1970s; Year of introduction: 2002 (Eli Lilly); Drug category: Anabolic agent; Main uses: Treatment of osteoporosis for patients with high risk of fractures; Drug category: First drug in its class, directly affecting osteoblasts and causing bone growth.

The maintenance of strong bones requires optimum calcium (Ca2+) and phosphate (P043") levels. The key regulators of these ions in the human body are parathyroid hormone and 1a,25-dihydroxy-vitamin D3 (see page 98). Parathyroid hormone, an 84 amino acid polypeptide secreted by the parathyroid glands, controls the concentration of calcium ions in extracellular fluid by regulating the supply of these ions from bone, and from reabsorption in the kidneys. Parathyroid hormone also stimulates the formation of calcitriol from its precursor, vitamin D3, which enhances absorption of calcium ions in the intestines. The secretion of parathyroid hormone varies inversely with plasma calcium ion concentration.

• Reabsorption

S3 i

Parathyroid Parathyroid J Intestines glands hormone Bone

Release Absorption

Sustained elevation of parathyroid hormone levels in the circulation causes bone loss. This is one consequence of hyperparathyroidism, a disease in which parathyroid hormone is produced in excess due to the overactivation of the thyroid glands.

Paradoxically, intermittent administration of parathyroid hormone stimulates bone formation. The timing of administration of the drug is critical, since exposure for a short period (< 2 h) leads to bone growth (anabolic response) whereas exposure for more than two hours induces bone loss (catabolic response). The beneficial effect of brief exposure to parathyroid hormone on bone formation may be the result of its stimulation of the transformation of stem cells in bone marrow into osteoblasts. Only the 27 amino acid N-terminal segment of parathyroid hormone is required for efficacy.1

Teriparatide is a synthetic parathyroid hormone segment containing the first 34 amino acid of the natural protein. This drug, developed by Eli Lilly and marketed under the name Forteo, was approved in 2002 for the treatment of osteoporosis. It is the first parathyroid hormone derivative on the market and also the first agent to act by affecting osteoblasts, thereby directly causing bone growth and an increase of bone density.2 Teriparatide is used as second-line therapy mainly in cases involving individuals with a history of osteoporosis-related fracture, or intolerant of other therapies. Since teriparatide is not orally absorbed, it is administered by injection.

1. N. Engl. J. Med. 2001, 344. 1434-1441; 2. Nat Rev. Drug Discov. 2003, 2, 257-258; Refs. p. 106




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