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Many drugs are removed from the circulation on passing through the lungs. However, in the majority of cases this occurs by retention of the drug in lung tissue rather than actual metabolism. This low activity of metabolic enzymes found in the lung occurs for two reasons. First, access to the metabolic enzymes in endothelial cells is closely controlled by highly specific uptake mechanisms that are vital to allow the highly selective metabolism of endogenous compounds.Second, it is possible that the oxidative systems responsible for drug metabolism elsewhere in the body are located mostly in the airways, thus preventing bloodborne drugs gaining access to them.Drugs that are basic (pKa .8) and lipophilic tend to be taken up in the pulmonary circulation, whereas acidic drugs preferentially bind to plasma proteins.Drug binding in the pulmonary circulation may act as a first pass filter for any drug administered intravenously. This drug reservoir within the lung may then be released slowly, or even give rise to rapid changes in plasma drug levels either when the binding sites become saturated or when one drug is displaced by a different drug with greater affinity for the same binding site

许多药物通过肺循环时被清除。然而，大多数情况下，这些药物只是滞留于肺组织中，而非真正的代谢。肺中发现代谢酶低活性的原因有二：首先，内皮细胞摄取代谢酶高度特异性，这极大造成了内源性化合物的高选择性代谢。其次，身体其他部位负责药物代谢的氧化系统可能主要位于气道，而血源性药物难以进入气道。碱性药物（pKa>8）以及亲脂性药物容易进入肺循环，而酸性药物则优先与血浆蛋白结合。任何静脉给药，肺循环中的药物结合可作为首过滤器。这种药物储存在肺内可缓慢释放，甚至在结合位点饱和、或一种药物被对同一结合位点具有更强亲和力的竞争性药物取代后，血药浓度会快速变化。