Smith B J, Phillips P J, Pannall P R, Cain H J, Leckie W J
Department of Thoracic Medicine, Queen Elizabeth Hospital, Woodville, South Australia.
Thorax. 1993 Sep;48(9):890-3. doi: 10.1136/thx.48.9.890.
There is evidence that patients with chronic obstructive airways disease and asthma who take inhaled steroids have a low bone density. As most of a drug given from a metered dose inhaler is actually swallowed, the possibility that swallowed beclomethasone dipropionate acts topically in the gut to impair calcium absorption was investigated. Such an effect, if sustained, may be a causative factor of long term bone loss.
A two week randomised, double blind, placebo controlled, crossover trial was performed in 12 normal volunteers. Subjects were randomly allocated to swallow beclomethasone dipropionate capsules (500 micrograms twice a day) or placebo for one week. The alternate capsule was given throughout the second week. At the end of each week, calcium absorption was assessed by a strontium absorption test. Serum parathyroid hormone, plasma calcium, and plasma phosphate concentrations were determined on the last two days of each week. Twenty four hour urinary calcium, hydroxyproline, and cortisol concentrations were measured for four successive days in each week.
All subjects completed the study. There was a 12% reduction in strontium absorption during the beclomethasone dipropionate ingestion week. There was also a 23% reduction in 24 hour urinary cortisol excretion during the same week.
Calcium absorption (measured by a strontium absorption test) was reduced by oral administration of beclomethasone dipropionate for one week. Decreased calcium absorption due to swallowed corticosteroid may contribute to side effects of inhaled steroids and further long term studies are needed.
有证据表明,患有慢性阻塞性气道疾病和哮喘的患者吸入类固醇后骨密度较低。由于定量吸入器喷出的大部分药物实际上会被吞咽,因此研究了吞咽的二丙酸倍氯米松是否会在肠道局部发挥作用,损害钙的吸收。如果这种作用持续存在,可能是长期骨质流失的一个致病因素。
对12名正常志愿者进行了一项为期两周的随机、双盲、安慰剂对照的交叉试验。受试者被随机分配,连续一周每天两次吞咽二丙酸倍氯米松胶囊(500微克)或安慰剂。在第二周服用另一种胶囊。在每周结束时,通过锶吸收试验评估钙的吸收情况。在每周的最后两天测定血清甲状旁腺激素、血浆钙和血浆磷酸盐浓度。在每周连续四天测量24小时尿钙、羟脯氨酸和皮质醇浓度。
所有受试者均完成研究。在摄入二丙酸倍氯米松的那一周,锶吸收降低了12%。在同一周内,24小时尿皮质醇排泄量也减少了23%。
口服二丙酸倍氯米松一周可降低钙的吸收(通过锶吸收试验测定)。因吞咽皮质类固醇导致的钙吸收减少可能是吸入类固醇副作用的一个原因,还需要进一步的长期研究。