The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism.
Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.
Goodman
William G
WG
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Hladik
Gerald A
GA
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Turner
Stewart A
SA
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Blaisdell
Peter W
PW
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Goodkin
David A
DA
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Liu
Wei
W
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Barri
Yousri M
YM
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Cohen
Raphael M
RM
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
Coburn
Jack W
JW
*Department of Medicine, UCLA School of Medicine, Los Angeles, California; Division of Nephrology, University of North Carolina, Chapel Hill, North Carolina; Amgen Inc., Thousand Oaks, California; VA Medical Center, Little Rock, Arkansas; Presbyterian Medical Center, Philadelphia, Pennsylvania;and VA Medical Center, West Los Angeles, California.
D000284:Administration, Oral; D000328:Adult; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D009281:Naphthalenes / Q000627:therapeutic use*; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000097:blood*; D006435:Renal Dialysis
D009281:Naphthalenes; D010281:Parathyroid Hormone; D002118:Calcium; D000069449:Cinacalcet