目的 探索奥曲肽注射液在儿童"口服给药"的可行性.方法 抗酸稳定性实验分为实验组(以pH 4.0～4.5的盐酸溶解奥曲肽)和对照组(以pH 7.0～7.5的0.9％NaCl溶解奥曲肽).将BN幼鼠按性别及体质量分级随机分配到奥曲肽皮下注射组(12 μg·kg-1·d-1,皮下注射)、奥曲肽口服给药组(12μg·kg-1·d-1,口服)和对照组(等量0.9％NaCl),每组10只.采集2例难治性腹泻患儿分别在奥曲肽皮下注射及口服给药1 h后血样标本,监测血药浓度情况.比较大鼠血药浓度和胃肠内浓度的差异,及2例患儿的血药浓度差异.用放射免疫法测定奥曲肽血药浓度.用免疫组化法检测大鼠肠道上奥曲肽浓度.结果 实验组和对照组的奥曲肽药物浓度分别为(810.71±1.91)和(816.55±5.60)ng·mL-1,在统计学上差异无统计学意义(P＞0.05).奥曲肽皮下注射组和奥曲肽口服给药组的奥曲肽阳性染色密度值(IOD值)分别为6.84±0.88和9.82±1.07,外周血中奥曲肽浓度分别为(26.07±12.19)和(3.53±0.76)ng·mL-1,在统计学上差异均有统计学意义(均P＜0.001).2例患儿口服和皮下注射的奥曲肽血药浓度分别为2.52～3.30和22.36～31.68 ng.mL-1.结论 奥曲肽"口服给药"会呈现"高胃肠浓度/低血药浓度"分布.高胃肠浓度可治疗儿童消化道局部疾患,且可避免注射痛苦.口服给药的低血药浓度有利于降低儿童生长抑制的全身性药物不良反应.
Objective To explore the feasibility of octreotide injection for"oral administration"in children.Methods The acid resistance stability experiment was divided into experimental group(dissolve octreotide in hydrochloric acid at pH 4.0-4.5)and control group(dissolve octreotide in 0.9％NaCl at pH 7.0-7.5).BN juvenile rats were randomly assigned to the subcutaneous injection group of octreotide(12 μg·kg-1·d-1,subcutaneous injection),the oral administration group of octreotide(12 μg·kg-1·d1-1,oral administration),and the control group(0.9％NaCl)based on gender and body mass grading,with 10 rats in each group.Collect blood samples from 2 children with refractory diarrhea after subcutaneous injection and oral administration of octreotide for 1 hour,and monitor the plasma concentration.Compare the differences in plasma and gastrointestinal concentrations in rats,as well as the differences in plasma concentration in two pediatric patients.Measure the plasma concentration of octreotide using radioimmunoassay.Detection of octreotide concentration in rat intestine by immunohistochemical method.Results The concentrations of octreotide in the experimental group and control group were(810.71±1.91)and(816.55±5.60)ng·mL-1,respectively,without statistically significant difference(P＞0.05).The integrated optical density(IOD)values of octreotide in the subcutaneous injection group and oral administration group were 6.84±0.88 and 9.82±1.07;the concentrations of octreotide in peripheral blood were(26.07±12.19)and(3.53±0.76)ng·mL-1,with statistical significance(all P＜0.001).The plasma concentration of octreotide administered orally and subcutaneously in two pediatric patients were 2.52-3.30 and 22.36-31.68 ng·mL-1.Conclusion"Oral administration"of octreotide exhibits a distribution of"high gastrointestinal concentration/low plasma concentration".High gastrointestinal concentration can treat local gastrointestinal diseases in children and avoid injection pain.Oral administration of low plasma concentration is beneficial for reducing systemic adverse drug reactions in children with growth inhibition.
何苗;谢咏梅;汪志凌
四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室,四川成都 610041||九○三医院儿科,四川江油 621700四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室,四川成都 610041
药学
奥曲肽;生长抑素;口服给药;皮下注射;儿童;血药浓度
octreotide;somatostatin;oral administration;subcutaneous injection;children;blood concentration
《中国临床药理学杂志》 2024 (005)
673-677 / 5
四川省科技厅自然科学基金资助项目(2019YFG0165);中央高校基本科研业务费专项资金资助项目(SCU2022F4080)
10.13699/j.cnki.1001-6821.2024.05.009
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