An oral cathepsin K inhibitor ONO-5334 inhibits N-terminal and C-terminal collagen crosslinks in serum and urine at similar plasma concentrations in postmenopausal women

摘要: Abstract Relationships between the plasma concentration of a cathepsin K inhibitor (ONO-5334) and inhibition bone resorption markers N-telopeptide type I collagen (NTX) C-telopeptide (CTX) in serum urinary NTX/creatinine CTX/creatinine were examined 10 postmenopausal women. The subjects received slow-release tablets 100 mg ONO-5534 under fasted or fed conditions study with crossover design. Inhibition NTX CTX levels concentrations ONO-5334 monitored at 0, 24, 48 168 h after dosing. Changes second morning urine evaluated on 1, 2 7 days Data analyzed using sigmoid maximal drug effect (Emax) models. inhibition, estimated Emax values, − 31.8% for NTX, − 53.1% CTX, − 67.2% NTX/creatinine, − 95.2% CTX/creatinine. half effective (EC50) confidence intervals 1.79 (1.01 to 3.16) ng/mL 2.07 (1.63 2.62) 1.85 (1.30 2.61) 1.98 (0.94 3.76) EC50 values four crosslinks did not significantly differ, as indicated by overlapping 95% intervals. highest signal-to-noise ratio was achieved 2-fold higher than that NTX. all correlated correlation coefficients ranging from 0.55 0.80. In conclusion, data slow-releasing women well fitted model. measured telopeptides, obtained level, but had ratio. telopeptides correlated. different telopeptides.