Sotaniemi E A, Niemelä O, Risteli L, Stenbäck F, Pelkonen R O, Lahtela J T, Risteli J
Clin Pharmacol Ther. 1986 Jul;40(1):46-55. doi: 10.1038/clpt.1986.138.
The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.
通过比较67例根据肝脏组织学分类的酒精性肝病患者血清III型前胶原氨基端前肽和基底膜（BM；IV型胶原7S结构域和层粘连蛋白）抗原浓度，评估纤维化对酒精性肝病药物代谢的影响。肝脏完整或为脂肪肝的酒精性肝病患者药物代谢快速或正常，胶原代谢正常。合并脂肪肝加纤维化或活动性肝硬化的酒精性肝病患者药物代谢降低，胶原和BM代谢的血清标志物水平升高。接受酶诱导剂治疗的非活动性肝硬化酒精性肝病患者的药物和胶原代谢参数有趋于正常的倾向。安替比林代谢与血清III型胶原和BM标志物水平有关，而与细胞色素P-450含量无关。纤维化过程，尤其是BM形成，会形成机械屏障，可能会阻止血液与肝细胞接触，从而延迟底物的可利用性。
