Okudaira K, Sawada Y, Sugiyama Y, Iga T, Hanano M
J Pharm Pharmacol. 1986 Feb;38(2):137-40. doi: 10.1111/j.2042-7158.1986.tb04529.x.
The mechanism of quinidine-induced decrease in the tissue distribution of digoxin to heart, liver and skeletal muscle has been examined in guinea-pigs. Quinidine, in the presence of adenosine-5'-triphosphate (ATP), inhibited the specific binding of digoxin in homogenates of heart, liver and muscle, while in the absence of ATP the inhibition was observed only in heart. The decrease in the tissue-to-plasma unbound concentration ratios (Kpu) of heart and muscle determined from in-vitro binding studies was comparable to that in the Kpu values observed in-vivo, while in liver it was not sufficient to account for the fall in Kpuin-vivo values. It is concluded that quinidine-induced decrease in the tissue distribution of digoxin in heart and muscle is due to inhibition of tissue binding of this drug, while that in liver could be partially attributed to the decrease in the tissue binding.
在豚鼠身上研究了奎尼丁导致地高辛在心脏、肝脏和骨骼肌组织分布减少的机制。在存在三磷酸腺苷（ATP）的情况下，奎尼丁抑制了地高辛在心脏、肝脏和肌肉匀浆中的特异性结合，而在不存在ATP时，仅在心脏中观察到抑制作用。通过体外结合研究确定的心脏和肌肉组织与血浆未结合浓度比（Kpu）的降低与体内观察到的Kpu值降低相当，而在肝脏中，这不足以解释体内Kpu值的下降。得出的结论是，奎尼丁导致地高辛在心脏和肌肉中的组织分布减少是由于该药物的组织结合受到抑制，而在肝脏中则可能部分归因于组织结合的减少。
