Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
Clin Ther. 2011 Oct;33(10):1516-23. doi: 10.1016/j.clinthera.2011.09.001. Epub 2011 Oct 2.
Children receiving glucocorticoids (GCs) are at an increased risk of fragility fractures. Conservative measures may be inadequate in treating low bone mass, giving rise to fractures in this population; as such, attention has turned to the use of bisphosphonates.
The goal of this study was to evaluate the bioavailability and single-dose tolerability of alendronate (ALN) in children receiving a stable dose of GCs.
Children (ages 4-17 years) receiving GC treatment for their chronic illnesses received intravenous (125 μg) and oral (35 mg) ALN in a 2-period, randomized crossover study, with doses separated by at least a 7-day washout period. Urine was collected for either 8 or 24 hours after drug administration to determine urinary excretion of ALN and bioavailability. Tolerability was assessed by continuous collection of adverse events reported during the study. The main outcome measures were total urinary excretion rates, oral bioavailability of ALN, and adverse events.
There were 12 patients in the 4- to 11-year-old group (mean age, 8.1 years; 5 girls) and 12 patients in the 12- to 17-year-old group (mean age, 14.3 years; 5 girls). The least-squares mean bioavailability (90% CI) for children aged 4 to 11 years (n = 12) was 0.43% (0.27-0.67) and for children aged 12 to 17 years (n = 12) it was 0.39% (0.26-0.60). The least-squares mean bioavailability for all ages combined was 0.41% (0.30-0.56), with no statistical difference between the 2 age groups. The total urinary excretion of ALN after the intravenous dose was similar between groups. Fifteen patients reported a total of 36 transient clinical nonserious adverse events, all of which were mild or moderate in intensity; the most common were headache (n = 13), abdominal pain (n = 3), limb, neck, or facial pain (n = 6), and ankle or knee swelling (n = 3).
The mean oral bioavailability of ALN was similar to previous pharmacokinetic studies in children with osteogenesis imperfecta and slightly lower than that observed in historical adult controls. Alendronate was generally well tolerated, with minor adverse events that resolved uneventfully. Elucidation of the full adverse-effect profile of this agent was limited by the single-dose nature of this study, and robust comparisons of the pharmacokinetics of ALN in different age groups may need a larger number of patients.
接受糖皮质激素（GCs）治疗的儿童发生脆性骨折的风险增加。对于这类人群，保守治疗可能不足以治疗低骨量，从而导致骨折；因此，人们开始关注双膦酸盐的应用。
本研究旨在评估儿童在接受稳定剂量 GCs 治疗时，阿伦膦酸钠（ALN）的生物利用度和单次剂量耐受性。
在这项 2 期、随机交叉研究中，接受慢性疾病 GC 治疗的儿童（4-17 岁）接受静脉（125μg）和口服（35mg）ALN 治疗，剂量间隔至少 7 天的洗脱期。在给药后 8 或 24 小时收集尿液，以确定 ALN 的尿液排泄率和生物利用度。通过连续收集研究期间报告的不良事件来评估耐受性。主要结局指标是总尿液排泄率、ALN 的口服生物利用度和不良事件。
4-11 岁组（平均年龄 8.1 岁；5 名女孩）有 12 例患者，12-17 岁组（平均年龄 14.3 岁；5 名女孩）有 12 例患者。4-11 岁儿童（n=12）的最小二乘均值生物利用度（90%CI）为 0.43%（0.27-0.67），12-17 岁儿童（n=12）的生物利用度为 0.39%（0.26-0.60）。所有年龄组的最小二乘均值生物利用度为 0.41%（0.30-0.56），2 个年龄组之间无统计学差异。静脉剂量后 ALN 的总尿液排泄量在组间相似。15 例患者共报告了 36 例短暂的临床非严重不良事件，均为轻度或中度；最常见的是头痛（n=13）、腹痛（n=3）、四肢、颈部或面部疼痛（n=6）、踝或膝关节肿胀（n=3）。
ALN 的口服生物利用度均值与既往成骨不全症儿童的药代动力学研究相似，略低于历史成人对照的观察值。阿伦膦酸钠总体耐受性良好，不良事件轻微且自行缓解。由于这项研究是单次剂量给药，因此对该药物的全不良反应谱的阐明受到限制，并且可能需要更多患者才能对不同年龄组的 ALN 药代动力学进行稳健比较。
