RELATION BETWEEN LIPOPHILICITY AND PHARMACOLOGICAL BEHAVIOR OF MINOCYCLINE, DOXYCYCLINE, TETRACYCLINE, AND OXYTETRACYCLINE IN DOGS
RELATION BETWEEN LIPOPHILICITY AND PHARMACOLOGICAL BEHAVIOR OF MINOCYCLINE, DOXYCYCLINE, TETRACYCLINE, AND OXYTETRACYCLINE IN DOGS
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DOI：
10.1128/aac.8.6.713
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发表时间：
1975-01-01
影响因子：
4.9
通讯作者：
WEINSTEIN, L
中科院分区：
文献类型：
--
作者：
BARZA, M;BROWN, RB;WEINSTEIN, L
本文对四种四环素类药物在犬体内进行了研究，以确定它们的亲脂性与其它药理特性之间的关系。脂溶性与动脉血浆药物平均浓度、肾脏摄取和排泄呈负相关，与胆汁浓度梯度(胆汁浓度/血清游离药物浓度)呈正相关。只有更亲脂的同系物米诺环素和多西环素以可检测的浓度通过血脑和血眼屏障。脑组织中米诺环素的平均浓度几乎是多西环素的3倍，差异有统计学意义(P=0.05~0.1)。亲脂性与抗菌素在肾髓质中的浓度呈负相关，而在肾皮质或肝脏中则不相关。当研究含有生理盐水、牛奶或10%Gelusil的肠循环时，唯一显示出显著腔内蓄积的组合是牛奶中的多西环素。这些结果表明，亲脂性与四环素类抗生素的许多(但不是全部)转运特性有关。
Four tetracyclines were studied in dogs to determine the relation between their lipophilicity and various other pharmacological characteristics. Lipid solubility correlated inversely with the mean concentration of drug in arterial plasma and renal uptake and excretion, and directly with the biliary concentration gradient (level in bile/level of free drug in serum). Only the more lipophilic congeners minocycline and doxycycline passed the blood-brain and blood-ocular barriers in detectable concentrations. Mean levels of minocycline in the brain exceeded those of doxycycline by almost threefold; the difference was of borderline statistical significance (P= 0.05 to 0.1). Lipophilicity correlated inversely with the concentration of antibiotic in renal medulla but not in renal cortex or in the liver. When intestinal loops containing saline, milk, or 10% Gelusil were studied, the only combination exhibiting striking intraluminal accumulation was doxycycline in milk. These results indicate that lipophilicity correlates with many, but not all, of the transport characteristics of tetracycline antibiotics.