Short-term inhibition of parathyroid hormone secretion by a calcium-receptor agonist in patients with primary hyperparathyroidism.
BACKGROUND
Surgery is the usual therapy for patients with primary hyperparathyroidism. We investigated the ability of a calcimimetic drug that inhibits parathyroid hormone secretion in vitro to decrease serum parathyroid hormone and calcium concentrations in patients with this disorder.


METHODS
We performed a randomized, placebo-controlled study of single oral doses of 4 to 160 mg of the calcium-receptor agonist drug R-568 in 20 postmenopausal women with mild primary hyperparathyroidism. At base line, the mean (+/-SE) serum calcium concentration was 10.7+/-0.2 mg per deciliter (2.67+/-0.05 mmol per liter). Serum parathyroid hormone and calcium were measured repeatedly after each dose, and safety was assessed.


RESULTS
Administration of R-568 resulted in a dose-dependent inhibition of parathyroid hormone secretion. The mean serum parathyroid hormone concentration, which was 77+/-11 pg per milliliter (18.8+/-2.7 pmol per liter; normal range, 16 to 65 pg per milliliter [3.9 to 15.9 pmol per liter) at base line, fell by 26+/-8 percent after 20 mg of R-568 (P=0.03), by 42+/-7 percent after 80 mg (P = 0.01), and by 51+/-5 percent after 160 mg (P=0.005). Serum ionized calcium concentrations fell only after the 160-mg dose, with the decrease closely following the decrease in the serum parathyroid hormone concentration.


CONCLUSIONS
The calcimimetic drug R-568 reduces serum parathyroid hormone and ionized calcium concentrations in postmenopausal women with primary hyperparathyroidism.
Silverberg
S J
SJ
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Bone
H G
HG
Marriott
T B
TB
Locker
F G
FG
Thys-Jacobs
S
S
Dziem
G
G
Kaatz
S
S
Sanguinetti
E L
EL
Bilezikian
J P
JP
D000368:Aged; D000814:Aniline Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000819:agonists* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D010627:Phenethylamines; D011437:Propylamines
D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010281:Parathyroid Hormone; D010627:Phenethylamines; D011437:Propylamines; D002118:Calcium