Schimmer Ralph C, Bauss Frieder
F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, Basel, Switzerland.
Clin Ther. 2003 Jan;25(1):19-34. doi: 10.1016/s0149-2918(03)90005-1.
Oral bisphosphonates are well established for the treatment and prevention of postmenopausal osteoporosis; however, they are poorly absorbed from the gastrointestinal (GI) tract and have been associated with GI adverse events. Thus, current dosing guidelines recommend that the patient not eat or lie down for at least 30 minutes after taking oral bisphosphonates, a requirement that is inconvenient and may be associated with reduced compliance. The drawbacks of these dosing requirements may be overcome either by reducing dosing frequency or by using alternative routes of administration.
Ibandronate is a potent nitrogen-containing bisphosphonate that can be given orally or IV, daily or intermittently, with a between-dose interval of up to 3 months. This article presents the results of published Phase II trials of the efficacy and safety profile of oral and IV ibandronate administered daily or intermittently to postmenopausal women with low bone mass.
MEDLINE was searched through January 2002 to identify all published Phase II clinical studies of oral and IV ibandronate in the treatment of post-menopausal osteoporosis.
In the 3 Phase II studies identified, marked reductions in biochemical markers of bone resorption (50%-70%) and bone formation (40%-50%) were seen to a similar and statistically significant extent with oral ibandronate 2.5 mg/d (P<0.001), oral ibandronate 20 mg QOD given for 12 doses at the start of each 3-monthly period (P<0.001), and injections of ibandronate 2 mg IV given every 3 months (P<0.01). All treatment regimens produced comparable significant increases in bone mineral density at the lumbar spine (P<0.01) and hip (P<0.05). Ibandronate was well tolerated when administered both orally and as an IV injection.
In these Phase II studies, oral or IV ibandronate, administered continuously or intermittently, reduced markers of bone turnover, significantly increased bone mineral density, and was well tolerated in the treatment of osteoporosis in postmenopausal women. The data from these studies provided the rationale for further investigation of ibandronate in larger longer-term Phase III studies evaluating its potential as an efficacious and flexible alternative to existing bisphosphonate regimens.
口服双膦酸盐类药物在治疗和预防绝经后骨质疏松症方面已得到充分认可;然而,它们在胃肠道的吸收较差,且与胃肠道不良事件有关。因此,目前的给药指南建议患者在服用口服双膦酸盐类药物后至少30分钟内不要进食或躺下,这一要求不方便,且可能与依从性降低有关。这些给药要求的缺点可以通过减少给药频率或采用替代给药途径来克服。
伊班膦酸钠是一种强效含氮双膦酸盐类药物,可口服或静脉注射,每日或间歇性给药,给药间隔长达3个月。本文介绍了已发表的II期试验结果,这些试验研究了每日或间歇性口服和静脉注射伊班膦酸钠对低骨量绝经后妇女的疗效和安全性。
检索MEDLINE截至2002年1月的文献,以确定所有已发表的关于口服和静脉注射伊班膦酸钠治疗绝经后骨质疏松症的II期临床研究。
在确定的3项II期研究中,口服2.5mg/d伊班膦酸钠(P<0.001)、每3个月开始时口服20mg伊班膦酸钠隔日1次共给药12剂(P<0.001)以及每3个月静脉注射2mg伊班膦酸钠(P<0.01),均能使骨吸收(50%-70%)和骨形成(40%-50%)的生化标志物显著降低,且降低程度相似且具有统计学意义。所有治疗方案均使腰椎(P<0.01)和髋部(P<0.05)的骨密度显著增加,且增加程度相当。口服和静脉注射伊班膦酸钠时耐受性均良好。
在这些II期研究中,连续或间歇性口服或静脉注射伊班膦酸钠可降低骨转换标志物,显著增加骨密度,且在治疗绝经后妇女骨质疏松症时耐受性良好。这些研究的数据为进一步开展更大规模、更长期的III期研究提供了理论依据,以评估伊班膦酸钠作为现有双膦酸盐治疗方案的有效且灵活替代方案的潜力。