3种上市鼻喷雾剂的鼻黏膜渗透性和安全性评价

Nasal Mucosal Permeability and Safety Evaluation of Three Approved Nasal Sprays

比较了临床上用于治疗变应性鼻炎的1种布地奈德鼻喷雾剂和2种糠酸莫米松鼻喷雾剂的鼻黏膜渗透性和药物动力学特征。本试验检测了这2种原料药的溶解度,以及3种上市鼻喷雾剂中药物对山羊鼻黏膜的渗透性和滞留性、给予大鼠后血浆和主要组织中药物浓度。结果显示,布地奈德在25℃超纯水中的溶解度为(18.92±0.03)μg/ml,而糠酸莫米松在水中的溶解度低于本研究分析方法的线性下限(5μg/ml)。鼻喷雾剂中布地奈德透山羊鼻黏膜的速率为1.07μg·cm^(-2)·h^(-1),而2种糠酸莫米松鼻喷雾剂中的透黏膜速率均低于0.77ng·cm^(-2)·h^(-1);滞留在山羊鼻黏膜中的布地奈德为19.27μg,也显著高于2种糠酸莫米松鼻喷雾剂的鼻黏膜药物滞留量(分别为2.27和2.61μg)。在将相当于5倍成人单日剂量的3种鼻喷雾剂给予大鼠后,大鼠血浆和各组织样品中的药物浓度均低于1ng/ml,说明吸收入血的药量非常少,3种上市鼻喷雾剂使用时安全性较高。

The nasal mucosal permeabilities and pharmacokinetic characteristics of one formulation of budesonide nasal spray and two formulations of mometasone furoate nasal spray for the treatment of allergic rhinitis in clinical practice were compared.In this study,the solubilities of two raw material drugs,the permeabilities of the drugs from three approved nasal sprays through goat nasal mucosa and retention amounts,and the drug concentrations in plasma and main tissues of the rats were determined.The results showed that the solubility of budesonide in ultrapure water at 25℃was(18.92±0.03)μg/ml,while the solubility of mometasone furoate was lower than the lower limit of linearity(5μg/ml).The permeation rate of budesonide from the nasal spray across goat nasal mucosa was 1.07μg·cm^(-2)·h^(-1),while the permeation rates of mometasone furoate from two formulations of the nasal spray were lower than 0.77 ng·cm^(-2)·h^(-1).The retention amount of budesonide in goat nasal mucosa was 19.27μg,which was significantly higher than those of mometasone furoate from two nasal sprays(2.27 and 2.61μg,respectively).After administration to rats(equivalent to 5 times of human daily dose),the drug concentrations in plasma and tissue samples were all lower than 1 ng/ml.It indicated that the amounts of the drugs which had been absorbed into the systemic circulation were low and the clinical safeties of three approved nasal sprays were high.