Barrett Joanne, Worth Eric, Bauss Frieder, Epstein Solomon
Roche Products Ltd., 40 Broadwater Road, Welwyn Garden City, Hertfordshire, AL7 3AY, United Kingdom.
J Clin Pharmacol. 2004 Sep;44(9):951-65. doi: 10.1177/0091270004267594.
Ibandronate is a potent nitrogen-containing bisphosphonate. It has a strong affinity for bone mineral and potently inhibits osteoclast-mediated bone resorption. Ibandronate is effective for the treatment of hypercalcemia of malignancy, metastatic bone disease, postmenopausal osteoporosis, corticosteroid-induced osteoporosis, and Paget's disease. Oral ibandronate is rapidly absorbed (t(max) < 1 hour), with a low bioavailability (0.63%) that is further reduced (by up to 90%) in the presence of food. Ibandronate has a wide therapeutic index and is not metabolized and, therefore, has a low potential for drug interactions. Given its metabolic stability, ibandronate is eliminated from the blood by partitioning into bone (40%-50%) and through renal clearance (CL(R) approximately 60 mL/min). The CL(R) of ibandronate is linearly related to creatinine clearance. The sequestration of ibandronate in bone (V(D) > 90 L) results in a multiphasic elimination (t((1/2)) range approximately 10-60 hours), characterized by the slow release of ibandronate from the bone compartment. The potency of ibandronate and its sequestration into bone allow ibandronate to be developed as oral and intravenous injection formulations that can be administered with convenient extended between-dose intervals.
伊班膦酸钠是一种强效含氮双膦酸盐。它对骨矿物质具有很强的亲和力，并能有效抑制破骨细胞介导的骨吸收。伊班膦酸钠可有效治疗恶性肿瘤引起的高钙血症、转移性骨病、绝经后骨质疏松症、糖皮质激素诱导的骨质疏松症和佩吉特病。口服伊班膦酸钠吸收迅速（t(max) < 1小时），生物利用度低（0.63%），在进食时会进一步降低（高达90%）。伊班膦酸钠具有较宽的治疗指数，且不被代谢，因此药物相互作用的可能性较低。鉴于其代谢稳定性，伊班膦酸钠通过分配进入骨骼（40%-50%）和经肾清除（CL(R)约为60 mL/min）而从血液中消除。伊班膦酸钠的CL(R)与肌酐清除率呈线性相关。伊班膦酸钠在骨骼中的潴留（V(D) > 90 L）导致多相消除（t((1/2))范围约为10-60小时），其特点是伊班膦酸钠从骨腔室缓慢释放。伊班膦酸钠的效力及其在骨骼中的潴留特性使其能够开发出口服和静脉注射制剂，且给药间隔时间可以延长，使用方便。
