平成 27 9 30 - pmda.go.jp

1 28 14 5 mg 27 9 30 28 28 8 15 5 mg 27 9 30 1 100 ml mg mg 4 6 8 2 1 1 5 mg 15 1 28 7 6 5 mg/100 mL 27 9 30 1 100 ml mg mg 5 mg 1 15 1 1.

2 3 2.. 3 3.. 3 4.. 8 5.. 8 6.. 9 7.. 13 8.. 50 9. 1 .. 51 2 Ae Cumulative amount of drug excreted in the urine AERS Adverse Event Reporting System AUC Area under the Concentration Time Curve BAP bone alkaline phosphatase CL clearance CLapp apparent total clearance CLcr creatinine clearance Cmax maximum plasma concentration CTX type I collagen cross-linked C-telopeptide 1 C- DPD deoxypyridinoline DXA dual energy X-ray absorptiometry 2

3 FAS Full Analysis Set FDA Food and Drug Administration FPPS farnesyl diphosphate synthase IC50 Half maximal inhibitory concentration 50% i-OC intact osteocalcin ITT Intent to treat LOCF Last Observation Carried Forward MedDRA Medical Dictionary for Regulatory Activities ICH mITT Modified Intent to treat NTX type I collagen cross-linked N-telopeptide I N- OC osteocalcin OVX ovariectomized P1NP type I procollagen-N-propeptide 1 -N- PPK population pharmacokinetics pQCT Peripheral Quantitative Computed Tomography PTH parathyroid hormone RANKL Receptor Activator of Nuclear Factor B Ligand NF B Rt amount retained in body SMI Structure Model Index TRACP-5b tartrate-resistant acid phosphatase 5b 5b YAM young adult mean 5 mg CT microfocus computed tomography 3 1.

4 5 mg Novartis Pharma AG 4mg 1) 2004 10 2006 4 2) 30 30 1 1 2007 8 10 2016 6 115 3) 4 1 1 1 1 1 1 1 4 1 1 1 2. 3.

5 In vivo 1) 4 mg/5 mL 4 mg/100 mL 4 mg/100mL 2012 9 2) 1 4 mg 15 1 1 4 mg 15 3 4 3) 2007 4 2008 12 2009 3 2009 5 2005 4 2008 9 2009 6 4 4 mg/5 mL J Bone Miner Res 2008; 23: 544-51 7 10 4 20 100 500 g/kg 200 g/kg 4) 4 OVX 7 10 4 OVX 32 Peripheral Quantitative Computed Tomography pQCT OVX 32 CT OVX g/kg OVX 16 4 g/kg OVX 32 OVX 100 g/kg OVX 32 20 g/kg 100 g/kg 100 g/kg OVX 3 20 g/kg OVX OVX 100 g/kg OVX 3 OVX OVX OC 5b

6 TRACP-5b 100 g/kg OVX 32 OVX OVX OC TRACP-5b OC OVX 20 TRACP-5b OVX 24 OVX OVX Structure Model Index SMI 100 g/kg SMI 20 g/kg 4) 5 4 g/kg OVX 100 g/kg 20 g/kg 100 g/kg OVX 100 g/kg 3 4 20 OVX g/kg 4) 1 52 4 20 1 52 52 2 DXA 51 52 52 OVX g/kg OVX OVX g/kg OVX 17 32 3 g/kg OVX g/kg OVX g/kg OVX OVX OC 16 g/kg OVX 51 DPD / 16 51 OVX g/kg OVX OVX OVX OVX

7 4 7 8 OVX g/kg 4) 1 69 8 4) 1 69 69 DXA 69 69 6 26 69 26 69 69 OVX g/kg OVX g/kg OVX 69 g/kg OVX 69 g/kg OVX 3 g/kg OVX OVX OC BAP I N- NTX / 69 g/kg OVX g/kg OVX

8 OVX g/kg OVX FPPS IC50 mol/L J Pharmacol Exp Ther 2001; 296: 235-42 4 mg/5 mL 16 6 FPPS 7 Bone 2006; 38: 628-36 300 500 4 mg/5 mL / OVX 2 OVX 32 OVX 100 g/kg 100 g/kg 5) AUC0-t 526 909 ng hr/mL AUC0-24 h 636 ng hr/mL 6) OVX / J Bone Miner Metab 2016; 34: 291-302 Calcif Tissue Int 2003; 72: 42-9 / J Clin Endocrinol Metab 2000; 85: 2197-202 Calcif Tissue Int 2004; 75: 469-76 32 1 J Bone Miner Res 2007.

9 22: 867-76 100 g/kg 1 2 4) 6 1 2 1 2 2 10 mm 44 J Bone Miner Res 2004; 19: 1698-705 100 g/kg 4) 2 2 4 6 18 44 X X 6 X 18 44 4 6 18 44 DXA 4 6 5) AUC0-t / 6) 5 mg 24 AUC0-24 h AK156-I-1 8 44 100 g/kg 2 2 AUC7) 1053 1818 ng hr/mL AUC0-24 h 636 ng hr/mL 6) L2310 8)

10 / 3/1057 3/1054 4. 4 mg/5 mL 5. 4 mg 15 3 4 1 5 mg 15 1 1 1 3 1 13 mg/kg 5 6 mg/kg 9 3 3 13 mg/kg mg/kg 6 mg/kg mg/kg mg/kg 3 6 mg/kg 5 9 7) AUC0-t / 8)