P. L. McCormack, G. Plosker
2012
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0
Influential Citations
11
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Drugs
Abstract
SummaryAbstractIbandronic acid (Bondronat®) is a potent, new-generation, nitrogen-containing bisphosphonate, available in both intravenous and oral formulations, which effectively inhibits osteoclast-mediated bone resorption. In clinical trials, the two formulations were equally effective in preventing skeletal-related events and improving quality of life in patients with bone metastases of breast cancer. Both intravenous and oral ibandronic acid reduced metastatic bone pain scores below baseline levels for up to 2 years. Oral ibandronic acid is administered as a single 50mg tablet taken once daily. It suppressed bone resorption in breast cancer patients with bone metastases to an extent similar to that observed with intravenous zoledronic acid. Both intravenous and oral ibandronic acid were well tolerated with no evidence of renal toxicity. Ibandronic acid is therefore a valuable addition to the bisphosphonates used in the treatment of bone metastases of breast cancer, offering high potency and the convenience of oral administration, combined with the absence of renal toxicity.Pharmacological PropertiesIbandronic acid inhibits the bone resorption activity of osteoclasts in osteolytic metastatic bone lesions. Being a nitrogen-containing bisphosphonate, it induces apoptosis in osteoclasts by interfering with the mevalonate pathway and inhibiting farnesyl pyrophosphate synthase. The antiresorptive potency of ibandronic acid in rats was 50-fold higher than that of pamidronic acid and 500-fold higher than that of clodronic acid.Ibandronic acid may also have direct antiproliferative effects on tumour cells. Animal and in vitro experiments suggest that the drug may inhibit tumour cell adhesion and invasion, induce tumour cell apoptosis, reduce the tumour burden and inhibit angiogenesis.Ibandronic acid rapidly binds to bone (40–50% of the circulating drug), particularly at sites of bone remodelling, or is eliminated. The absorption of oral ibandronic acid is poor and severely impaired by food and drink. The oral bioavailability was 0.44% when administered 30 minutes prior to food or drink. Ibandronic acid is not metabolised and any drug not bound to bone is eliminated by the kidneys and excreted unchanged in the urine with a half-life of approximately 10–14 hours after intravenous administration.Therapeutic EfficacyIntravenous ibandronic acid 6mg every 3–4 weeks in patients with breast cancer and bone metastases produced a significant 20% reduction relative to placebo in the overall skeletal morbidity period rate (SMPR) over 96 weeks, which equated to a 40% reduction in the relative risk of skeletal-related events. Intravenous ibandronic acid 2mg was not significantly different from placebo.Oral ibandronic acid 50mg once daily for 96 weeks in patients with bone metastases of breast cancer similarly reduced the overall SMPR by 18% compared with placebo, equating to a reduction in the relative risk of skeletal-related events of 38% relative to placebo. Clinical benefit was accompanied by improvements in biochemical markers of bone turnover.Intravenous ibandronic acid 6mg and oral ibandronic acid 50mg each significantly improved patients’ health-related quality of life in the 96-week clinical trials.Oral ibandronic acid 50mg once daily and intravenous zoledronic acid 4mg every 4 weeks similarly and significantly reduced biochemical markers of bone turnover after 12 weeks in patients with breast cancer and bone metastases, suggesting they would have similar efficacy in preventing skeletal-related events.TolerabilityIbandronic acid was well tolerated throughout 4 years of use. In clinical trials, the only notable adverse events with an incidence higher than placebo were flu-like syndrome, myalgia and diarrhoea with intravenous ibandronic acid 6mg and hypocalcaemia, dyspepsia, nausea and oesophagitis with oral ibandronic acid 50mg. There was no evidence of renal toxicity with intravenous or oral ibandronic acid.