Raab W, Gmeiner B
Arch Dermatol Res (1975). 1975 Nov 14;254(1):87-93. doi: 10.1007/BF00561539.
By in vitro assay, 6 important enzymatic activities of human skin homogenates were determined following an incubation with D-penicillamine in concentrations between 10(-4) and 10 mg/ml, i.e. 67 X 10(-5) and 67 mM/l. The following enzymatic activities were recorded: lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alkaline phosphatase (AP), acid phosphatase (AcP), and "leucine aminopeptidase" (LAP). A dose-dependent activation by D-penicillamine occurred in the case of G-6-PDH- and AcP-activities, a dose-dependent inhibition by D-penicillamine was found with AP- and GAPDH-activities. LDH- and LAP-activities remained unchanged in the presence of D-penicillamine in concentrations up to 10 mg/ml (67 mM/l). From the data of pharmacokinetic studies in rats it may be concluded that concentrations of D-penicillamine which influence enzymatic activities may easily be reached in vivo, under the conditions of treating rheumatoid arthritis and Morbus Wilson. The biochemical actions of D-penicillamine are briefly discussed with secial regard to dermatological therapy and dermatological unwanted side-effects.
通过体外试验,在人皮肤匀浆与浓度介于10⁻⁴至10毫克/毫升(即67×10⁻⁵至67毫摩尔/升)的D-青霉胺孵育后,测定了6种重要的酶活性。记录了以下酶活性:乳酸脱氢酶(LDH)、葡萄糖-6-磷酸脱氢酶(G-6-PDH)、甘油醛-3-磷酸脱氢酶(GAPDH)、碱性磷酸酶(AP)、酸性磷酸酶(AcP)和“亮氨酸氨肽酶”(LAP)。D-青霉胺对G-6-PDH和AcP活性呈剂量依赖性激活,对AP和GAPDH活性则呈剂量依赖性抑制。在浓度高达10毫克/毫升(67毫摩尔/升)的D-青霉胺存在下,LDH和LAP活性保持不变。从大鼠的药代动力学研究数据可以得出结论,在治疗类风湿性关节炎和威尔逊氏病的情况下,体内可能很容易达到影响酶活性的D-青霉胺浓度。简要讨论了D-青霉胺的生化作用,特别关注了皮肤科治疗和皮肤科不良副作用。