D 3 (cholecalciferol)

Transcript

1 D (secondary hyperparathyroidism) [1,25-(OH) 2 D 3 (calcitriol)] 25-hydroxyvitamin D 40 ml/min D(vitamin D receptor) D D [1] (tertiary hyperparathyroidism) [2] ( )D (calcimimetics) D D D D D 7-dehydrocholesterol D 3 (cholecalciferol) 200 D [3] D /379.indd /9/20 2:31:27 PM

2 D D D 2 (ergocalciferol)d 3 D (chylomicrons) D (25-hydroxylase)25-hydroxyvitamin D(calcidiol)D Calcidiol 1%D 14 D D D calcidiol [4] calcidol P-450 alcohol barbiturates phenytoin Calcidiol D D D calcidiold calcidiol (1-α-hydroxylase 24-α-hydroxylase) calcidiol 1,25-dihydroxyvitamin D( D)24,25-dihydroxyvitamin D(D) 1-α-hydroxylase D [5] calcidiol (1-α-hydroxylase 24-α-hydroxylase)1-α-hydroxylase [6] () 1-α-hydroxylase calcidiol 24-hydroxylase24-hydroxylase (renal osteodystrophy) D D (calcium-sensing receptor) (intact parathyroid hormone) D D D D ( 300 pg/ml) D /379.indd /9/20 2:31:28 PM

3 D D (VDR knockout mice) D [7] (positive calcium balance) ( ) (tolerance) 7 8 μg/week (1 μg/day) [8] ( μg/day) [8] (pulse oral) [9] [10] ( pg/ml ) (alkaline phosphatase) μg μg1.5 μg 1 2 μg 2.5 meq/l 12 mg/dl pg/ml 1 2 μg pg/ml 2 4 μg D D /379.indd /9/20 2:31:29 PM

4 (electron-beam CT) [11] D D Paricalcitol 19-nor-1α,25-(OH) 2 D 2 Zemplar Pericalcitol Calcitriol pg/ml 75 [12] 50% ( or 11.5 mg/dl [2.0 mmol/l]) ( 75) Pericalcitol Calcitriol Pericalcitol Calcitriol ( 60%) Pericalcitol 50% (1523 ) Pericalcitol (29021 ) Calcitriol (38378 ) [13] Pericalcitol Calcitriol (18% 22.3%)12 Pericalcitol Calcitriol 59% 57% Calcitriol Pericalcitol(14862 )Pericalcitol Calcitriol (1621 )(survival rate) 7 3 % 6 4 % Pericalcitol Pericalcitol μg/kg 2 4 μg 0.24 μg/kg (16.8μg) 30% 30% 75 [14,15,16] Doxercalciferol 1α(OH)D 2 Hectorol1α,25- (OH) 2 D 2 10 μg ( ) pg/ml 50%8 2.5 μg 100 pg/ml μg [15] 400 pg/ml4 μg 50% /379.indd /9/20 2:31:29 PM

5 300 pg/ml μg pg/ml100 pg/ml 1 μg Alfacacidol (Alfarol, Onealfa) 1α(OH)D 3 1α,25-(OH) 2 D 3 50% 75% 3 μg μg [15] o x a c a l c i t r i o l ( O C T ) 22-oxao1,25(OH) 2 D 3 Maxacalcitol [15] D D (nodular hyperplasia) [18] pericalcitol D (30 59 ml/min ) 70 pg/ml (15 29 ml/ min) 110 pg/ml D [19,20] 4.6 mg/dl (1.49 mmol/l)9.5 mg/dl (2.37 mmol/l)d D D 圖 1. 鈣三醇及其他維生素 D 衍生物之化學結構 (Chemical structure of 1,25(OH) 2 D 3 and several vitamin D analogs) /379.indd /9/20 2:31:30 PM

6 1. D ; a from references 17 Calcitriol Paricalcitol Calcijex ( ) Zemplar ( ) 1,25-(OH) 2 D 3 19-nor-1α,25-(OH) 2 D 2 Ampoule ; 5 microgram/milliliter 1 milliliter per ampoule Ampoule ; 1 or 2 microgram/milliliter 1 milliliter per ampoule (HD patient) (IV) a 15 a ( Calcitriol 1) ( Calcitriol 1) 1 1/3 1 1/10 2. D Alfacacidol Calcitriol () Alfarol () Rocatrol() Onealfa () () (0.25 ug) (0.25 ug 0.50 ug) (0.50 ug) 1. Denda M, Finch J, Brown AJ, et al: 1.25-Dihydroxyvitamin D3 and 22-oxacalcitriol prevent the decrease in vitamin D receptor content in the parathyroid glands of uremic rats. Kidney Int 1996; 50: Goodman WG, Veldhuis JD, Belin TR, et al: Calcium-sensing by parathyroid glands in secondary hyperparathyroidism. J Clin Endocrinol Metab 1998; 83: Haddad JG: Vitamin D-solar rays, the Milky Way, or both? N Engl J Med 1992; 326: DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80: 1689S. 5. Zehnder D, Bland R, Walker EA, et al: Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in the human kidney. J Am Soc Nephrol 1999; 10: Takeyama K, Kitanaka S, Sato T, et al: 25-hydroxyvitamin D3 1a-hydroxylase and vitamin D synthesis. Science 1997; 277: Li YC, Amling M, Pirro AE, et al: Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology 1998; 139: /379.indd /9/20 2:31:31 PM

7 8. Quarles LD, Davidai GA, Schwab SJ, et al: Oral calcitriol and calcium: Efficient therapy for uremic hyperparathyroidism. Kidney Int 1988; 34: Moe SM, Kraus MA, Gassensmith CM, et al: Safety and efficacy of pulse and daily calcitriol in patients on CAPD: A randomized trial. Nephrol Dial Transplant 1998; 13: Gadallah, MF, Arora, N, Torres, C, et al: Pulse oral versus pulse intraperitoneal calcitriol: a comparison of efficacy in the treatment of hyperparathyroidism and renal osteodystrophy in peritoneal dialysis patients. Adv Perit Dial 2000; 16: Goodman WG, Goldin J, et al: Coronary-Artery Calcification in Young Adults with End-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: Sprague, SM, Llach, F, Amdahl, M, et al: Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 2003; 63: Teng M, Wolf M, Lowrie E, Ofsthun N: Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003; 349: Robinson DM, Scott LJ: Paricalcitol: a review of its use in the management of secondary hyperparathyroidism. Drugs 2005; 65(4): pp Slatopolsky E, Finch J, Brown A: New vitamin D analogs. Kidney Intermational 2003; Vol. 63,Supplement 85: S George R. Ballie, Curtis AJ: Comparative Review of the Pharmacokinetics of Vitamin D Analogues. Seminars in Dialysis 2002 pp Fukuda N, Tanaka H, Tominaga Y, et al: Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest 1993; 92: K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Am J Kidney Dis 2003; 42(Suppl 3): S Tanenbaum ND, Quarles LD, Cronin RE: Calcitriol,vitamin D analogs,and calcimimetics to control hyperparathyroidism in chronic renal failure. UpToDate /379.indd /9/20 2:31:32 PM