A semimechanistic model of the time-course of release of PTH into plasma following administration of the calcilytic JTT-305/MK-5442 in humans

Journal of Bone and Mineral Research

Volumn 28, Issue 8, 2013, Pages 1830-1836

  Cabal, Antonio ^a   Mehta, Khamir ^a   Ross, David S ^b   Shrestha, Rajiv P ^c   Comisar, Wendy ^a   Denker, Andrew ^a   Pai, Sudhakar M ^d   Ishikawa, Tomohiro ^e  

^a MERCK RESEARCH LABORATORIES   (United States)

^b ROCHESTER INSTITUTE OF TECHNOLOGY   (United States)

^c University of Massachusetts   (United States)

^d Akros Pharma Inc   (United States)

^e JAPAN TOBACCO INC   (Japan)

Author keywords

calcilytic; JTT 305 MK 5442; mechanistic PK PD; modeling; osteoporosis

Indexed keywords

CALCIUM SENSING RECEPTOR; JTT 305; MK 5442; PARATHYROID HORMONE; UNCLASSIFIED DRUG;

ARTICLE; CALCIUM BINDING; CONCENTRATION (PARAMETERS); HUMAN; KINETICS; PARATHYROID HORMONE RELEASE; POSTMENOPAUSE; POSTMENOPAUSE OSTEOPOROSIS; UNITED STATES;

EID: 84881256444     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.1900     Document Type: Article

References (24)

1. Fukumoto S, Nakamura T, Nishizawa Y, Hayahi M, Matsumoto T., Randomized, single-blinded placebo-controlled study of a novel calcilytic, JTT-305, in patients with postmenopausal osteoporosis. J Bone Miner Res. 2009; 24 (Suppl 1): S40.
2. Fukumoto S., [Antagonist for calcium-sensing receptor. JTT-305/MK-5442]. Clin Calcium. 2011 Jan; 21 (1): 89-93. Japanese.
3. Kimura S, Nakagawa T, Okamoto Y, Ishida Y, Matsuo Y, Shinagawa Y, Hayashi M., The effect of JTT-305 (MK-5442), an orally active calcium-sensing receptor antagonist, on calcium metabolism in parathyroidectomized rats. J Bone Miner Res. 2011; 26 (Suppl 1): S149.
4. Kimura S, Nakagawa T, Matsuo Y, Ishida Y, Okamoto Y, Hayashi M., JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats. Eur J Pharmacol. 2011; 668: 331-6.
5. Shinagawa Y, Inoue T, Kasushima T, Kihuchi T, Ikenogami T, Ogawa N, Fukuda K, Hirata K, Harada K, Takagi M, Nakagawa T, Kimura S, Matsuo Y, Maekawa M, Hayashi M, Soejima Y, Takahashi M, Shindo M, Hashimoto H., Discovery of a potent and short-acting oral calcilytic with pulsatile secretion of parathyroid hormone. ACS Med Chem Lett. 2011; 2: 238-242.
6. Frolik CA, Black EC, Cain RL, Satterwhite JH, Brown-Augsburger PL, Sato M, Hock JM., Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure. Bone. 2003; 33: 372-379.
7. Hock JM, Gera I., Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone. J Bone Miner Res. 1992; 7: 65-72.
8. Jilka RL., Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone. 2007; 40: 1434-1446.
9. Schwietert HR, Groen EW, Sollie FA, Jonkman JH., Single-dose subcutaneous administration of recombinant human parathyroid hormone [rhPTH(1-84)] in healthy postmenopausal volunteers. Clin Pharmacol Ther. 1997; 61: 360-376.
10. Moen MD, Scott LJ., Recombinant full-length parathyroid hormone (1-84). Drugs. 2006; 66: 2371-2381.
11. Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, Matriano JA, Gaumer K, Daddona PE., Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women. J Clin Endocrinol Metab. 2010; 95: 151-158.
12. Shrestha RP, Hollot CV, Chipkin SR, Schmitt CP, Chait Y., A mathematical model of parathyroid hormone response to acute changes in plasma ionized calcium concentration in humans. Math Biosci. 2010; 226: 46-57.
13. Yano S, Brown EM., The calcium sensing receptor. In:, Naveh-Many T, editor. Molecular biology of the parathyroid. New York: Kluwer Academic/Plenum; 2005. p. 44-56.
14. Brown EM., Calcium receptor and regulation of parathyroid hormone secretion. Rev Endocr Metab Disord. 2000; 1: 307-315.
15. Goodman WG., Recent developments in the management of secondary hyperparathyroidism. Kidney Int. 2001; 59: 1187-1201.
16. Joseph F, Chan BY, Durham BH, Ahmad AM, Vinjamuri S, Gallagher JA, Vora JP, Fraser WD., The circadian rhythm of osteoprotegerin and its association with parathyroid hormone secretion. J Clin Endocrinol Metab. 2007; 92: 3230-3238.
17. Abraham AK, Mager DE, Gao X, Li M, Healy DR, Maurer TS., Mechanism-based pharmacokinetic/pharmacodynamic model of parathyroid hormone-calcium homeostasis in rats and humans. J Pharmacol Exp Ther. 2009; 330: 169-178.
18. Ritchie CK, Cohn DV, Meercklein PB, Fitzpatric LA., Individual parathyroid cells exhibit cyclic secretion of parathyroid hormone and chromogranin-A (as measured by a novel sequential hemolytic plaque assay). Endocrinology. 1992; 131: 2638-2642.
19. Sharma A, Ebling WF, Jusko WJ., Precursor-dependent indirect pharmacodynamic response model for tolerance and rebound phenomena. J Pharm Sci. 1998; 87: 1577-1584.
20. Mager DE, Wyska E, Jusko WJ., Diversity of mechanism-based pharmacodynamic models. Drug Metab Dispos. 2003; 31: 510-518.
21. Canalis E, Giustina A, Bilezikian JP., Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007; 357: 905-916.
22. Nemeth EF., The search for calcium receptor antagonists (calcilytics). J Mol Endocrinol. 2002; 29: 15-21.
23. Fukumoto S, Nakamura T, Nishizawa Y, Matsumoto T., Randomized, double-blinded placebo-controlled study of a calcilytic compound, JTT-305, in patients with postmenopausal osteoporosis. Bone. 2011; 48: S76.
24. Fitzpatrick LA, Dabrowski CE, Cicconetti G, Gordon DN, Papapoulos S, Bone HG III, Bilezikian JP., The effects of ronacaleret, a calcium-sensing receptor antagonist, on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mineral density. J Clin Endocrinol Metab. 2011; 96: 2441-9.