Mialon P, Charfi R, Regnard J, Lockhart A, Dinh-Xuan A T
Laboratoire de Physiologie, Faculté de Médecine, Brest, France.
Eur J Clin Pharmacol. 1993;45(4):347-51. doi: 10.1007/BF00265953.
Previous publications suggest that prolonged inhalation of frusemide (F) does not cause a fall in the nasal transepithelial potential difference (PD) whereas locally deposited F does. In an attempt to reconcile these observations, we have measured the effect of inhalation through the nose and local deposition of F, amiloride (A), bumetanide (B) and salbutamol (S) on nasal PD in 7 healthy male volunteers in a randomised, double blind study. Solutions of drugs ranging from 10(-6) M to 10(-3) M (3 x 10(-8) M to 3 x 10(-5) M for B) in phosphate buffered saline 0.5 ml (PBS) were sequentially deposited in both nostrils, and nasal PD was measured 5 min after each dose. In 10 further volunteers, 10(-2) M solutions of A, F and S (3 x 10(-4) M for B) 5 ml were nebulised through the nose for 15 min, when nasal PD was measured. Resting PD was similar in the left and right nostrils averaging -17.1 mV (lumen negative). Placebo, inhaled of deposited B and S, and inhaled F did not change nasal PD. Topically deposited F significantly lowered PDmax in a dose-dependent manner [10(-4) M, -12% from baseline; 10(-3) M, -24%] as did the more potent A [10(-5) M, -19%; 10(-4) M, -31%; 10(-3) M, -47%]. Nebulised A (10(-2) M) had the same effect on nasal PD as deposited A (10(-4) M). The effects of locally deposited F and A (10(-3) M) on nasal PD were additive.(ABSTRACT TRUNCATED AT 250 WORDS)
以往的出版物表明，长时间吸入速尿（F）不会导致鼻跨上皮电位差（PD）下降，而局部沉积的F则会。为了协调这些观察结果，我们在一项随机、双盲研究中，测量了7名健康男性志愿者通过鼻腔吸入以及F、阿米洛利（A）、布美他尼（B）和沙丁胺醇（S）局部沉积对鼻PD的影响。将浓度范围为10⁻⁶M至10⁻³M（B为3×10⁻⁸M至3×10⁻⁵M）的药物溶液0.5毫升于磷酸盐缓冲盐水（PBS）中，依次滴入双侧鼻孔，每次给药后5分钟测量鼻PD。在另外10名志愿者中，将10⁻²M的A、F和S溶液（B为3×10⁻⁴M）5毫升通过鼻腔雾化15分钟后测量鼻PD。左右鼻孔的静息PD相似，平均为-17.1毫伏（管腔为负）。安慰剂、吸入或沉积的B和S以及吸入的F均未改变鼻PD。局部沉积的F以剂量依赖性方式显著降低PDmax[10⁻⁴M，较基线降低12%；10⁻³M，降低24%]，更强效的A也是如此[10⁻⁵M，降低19%；10⁻⁴M，降低31%；10⁻³M，降低47%]。雾化的A（10⁻²M）对鼻PD的影响与沉积的A（10⁻⁴M）相同。局部沉积的F和A（10⁻³M）对鼻PD的影响具有相加性。（摘要截短于250字）
