1. TERIPARATIDE DB06285 C181H291N55O51S2 4.12 kDa CATEGORY
Bone Density Conservation Agents

2. DESCRIPTION
Teriparatide (recombinant human parathyroid hormone) is a potent anabolic agent used in the treatment of osteoporosis. It is manufactured and marketed by Eli Lilly and Company.
INDICATION
For the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. Also used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture.
PHARMACODYNAMICS
Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density.

3. MECHANISM OF ACTION
Teriparatide is the portion of human parathyroid hormone (PTH),amino acid sequence 1 through 34 of the complete molecule which contains amino acid sequence 1 to 84.
TOXICITY
Effects of overexposure may include headaches, dizziness, dizziness, decreased blood pressured, decreased fetal survival, leg cramps, changes in clinical chemistry including increased in blood levels of calcium, decreased serum phosphorous, and increased urinary calcium and phosphorus.
METABOLISM
Hepatic
ABSORPTION
Bioavailability is 95% following subcutaneous injection.

4. ROUTE OF ELIMINATION
Peripheral metabolism of PTH is believed to occur by non-specific enzymatic mechanisms in the liver followed by excretion via the kidneys. The 24-hour urine excretion of calcium was reduced by a clinically unimportant amount (15%).
VOLUME OF DISTRIBUTION = L/kg
CLEARANCE = 62 L/hr [Women] 94 L/hr [Men]

5. SEQUENCE
Parathyroid hormone precursor - Homo sapiens (1-34)SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF
TARGETS
Parathyroid hormone/parathyroid hormone-related peptide receptor

6. Forteo/Forsteo IV and SC
FORTEO (teriparatide [rDNA origin] injection) contains recombinant human parathyroid hormone (1-34), and is also called rhPTH (1-34). It has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone.
DOSAGE:
20 mcg subcutaneously once a day.

7. FORMULATION
FORTEO is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.
HALF-LIFE: 5 min (IV) and 1 h (subcutaneous)
CLEARANCE: 62 L/h (women) and 94 L/h (men)

8. ADVERSE REACTION:
Feeling light-headed or fainting every time you inject this medicine;
fast or pounding heartbeats every time you inject this medicine; or
nausea, vomiting, constipation, and muscle weakness.
PATENT
Country Patent Number Approved Expires (estimated)
Canada
Canada
United States
United States

9. REFERENCE
Stroup J, Kane MP, Abu-Baker AM: Teriparatide in the treatment of osteoporosis. Am J Health Syst Pharm Mar 15;65(6): Pubmed
Close P, Neuprez A, Reginster JY: Developments in the pharmacotherapeutic management of osteoporosis. Expert Opin Pharmacother Aug;7(12): Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res Jan 1;30(1):412-5