Milne M D
Proc R Soc Med. 1965 Nov;58(11 Part 2):961-3. doi: 10.1177/003591576505811P204.
Changes in acid-base balance have a profound influence on many aspects of the action of drugs. This is illustrated by data on the absorption of drugs from the stomach and intestine, in changes in distribution of drugs between plasma and cells, and the effect of change in urinary pH.As a general principle, these changes in the pharmacology of weak acids and bases are governed by physicochemical principles, which influence the proportion of the ionized and unionized components according to the pH of the medium and also to the peculiar property of biological membranes which allow the free passage of the lipoid-soluble unionized component and impede transfer of the water-soluble ionized fraction.Lipoid-soluble weak acids are excreted at higher clearances in alkaline urine, and conversely weak bases in acid urine. This is shown to be of practical importance in the treatment of poisoning, in the diagnosis of addiction to drugs and in studies of drug metabolism. In general, the excretion of natural metabolites is less likely to be influenced by urinary pH, as these substances are usually less lipoid-soluble than many widely used drugs. pH-dependent excretion is, however, of practical importance in relation to the urinary content of many indolic metabolites and also in the excretion of pigments derived from the degradation of haemoglobin. Urobilinogen excretion is certainly pH-dependent, a higher clearance rate occurring in alkaline urine. However, work is necessary to decide whether some of the porphyrins also show this important physiological property.
酸碱平衡的变化对药物作用的许多方面都有深远影响。这一点从药物在胃和肠道的吸收数据、药物在血浆和细胞间分布的变化以及尿液pH值变化的影响中得到了体现。一般来说，弱酸和弱碱药理学的这些变化受物理化学原理支配，这些原理根据介质的pH值影响离子化和非离子化成分的比例，也受生物膜特性的影响，生物膜允许脂溶性非离子化成分自由通过，而阻碍水溶性离子化部分的转运。脂溶性弱酸在碱性尿液中的清除率较高，相反，弱碱在酸性尿液中的清除率较高。这在中毒治疗、药物成瘾诊断和药物代谢研究中具有实际重要性。一般来说，天然代谢产物的排泄受尿液pH值影响的可能性较小，因为这些物质通常比许多广泛使用的药物脂溶性更低。然而，pH依赖性排泄在许多吲哚代谢产物的尿液含量方面以及血红蛋白降解产生的色素排泄方面具有实际重要性。尿胆原的排泄肯定是pH依赖性的，在碱性尿液中清除率更高。然而，还需要开展工作来确定某些卟啉是否也表现出这种重要的生理特性。
