Lüllmann H, Martins B S, Peters T
Br J Anaesth. 1985 Oct;57(10):1012-7. doi: 10.1093/bja/57.10.1012.
The influence of the pH of the incubation medium on the cellular accumulation of tritiated fentanyl, lofentanil, and alfentanil was investigated in isolated guinea pig atria. Fentanyl and lofentanil accumulated in atrial tissue up to about 30- and 50-fold, respectively. The amount of drug bound when equilibrium was attained was found to be dependent upon the pH of the medium. By plotting binding equilibria v. pH of the bath, curves were obtained which resembled titration curves. Half-maximal binding was attained at pH values close to the pKa values of fentanyl and lofentanil. Alfentanil was found to accumulate less. The uptake by the tissue was strongly proportional to the extracellular concentration. Atria equilibrated with fentanyl at pH 8.5 released the compound rapidly when exposed to a pH of 7.0, even in the continuous presence of fentanyl in the bath. The consequences of the findings for in vivo conditions are discussed with respect to a possible augmentation of the actions of fentanyl by respiratory acidosis.
在离体豚鼠心房中研究了孵育介质的pH值对氚标记芬太尼、洛芬太尼和阿芬太尼细胞蓄积的影响。芬太尼和洛芬太尼分别在心房组织中蓄积至约30倍和50倍。发现达到平衡时结合的药物量取决于介质的pH值。通过绘制结合平衡对浴液pH值的曲线，得到了类似于滴定曲线的曲线。在接近芬太尼和洛芬太尼pKa值的pH值下达到最大结合量的一半。发现阿芬太尼的蓄积较少。组织摄取与细胞外浓度密切相关。在pH 8.5下用芬太尼平衡的心房，当暴露于pH 7.0时，即使浴液中持续存在芬太尼，也会迅速释放该化合物。就呼吸性酸中毒可能增强芬太尼作用而言，讨论了这些发现对体内情况的影响。
