Penicillamine exists as 2 stereoisomers, but only the D-isomer is used therapeutically. Its chemical reactivity derives from its functional groups, of which the thiol group seems the most important. It is difficult to determine penicillamine in biological fluids because of its instability, the presence of endogenous compounds with a thiol function, and the various chemical forms in which it occurs, namely reduced free penicillamine, penicillamine bound to proteins, and internal (P-S-S-P) and mixed (P-S-S-C) disulphides. The earliest assay methods (colourimetry, isotopic methods, gas-phase chromatography) were neither sensitive nor specific. High performance liquid chromatography with electrochemical detection has led to a more specific assay for D-penicillamine, with detection based on either derivatisation reactions or on electro-oxidisation of the thiol function. With dual-electrode detectors (Au/Hg) disulphides can be assayed directly. D-penicillamine is absorbed rapidly but incompletely (40 to 70%) in the intestine, with wide interindividual variations. Food, antacids and, in particular, iron reduce absorption of the drug. Its bioavailability is also dramatically decreased in patients with malabsorption states. The peak plasma concentration occurs at 1 to 3 hours after ingestion, regardless of dose, and is of the order of 1 to 2 mg/L after an oral dose of 250 mg; some investigators have reported a double peak in plasma, which is probably not due to an enterohepatic cycle. The concentration in plasma then decreases rapidly, generally following a biphasic curve. When long term treatment is discontinued, there is a slow elimination phase lasting 4 to 6 days, which suggests that there is a 'deep compartment' or 'slow pool of the drug reversibly bound to tissues', particularly the skin. This may explain the persistence of its therapeutic effect and the occurrence of undesirable side effects after treatment has been stopped. During long term treatment plasma concentrations are highly variable between individuals. They do not seem to be correlated with the activity or the toxicity of D-penicillamine in patients with rheumatoid arthritis. More than 80% of plasma D-penicillamine is bound to proteins, particularly albumin. The rest is mainly in the free reduced form or as disulphides. Only a small portion of the dose is metabolised in the liver to S-methyl-D-penicillamine. The route of elimination is mainly renal; disulphides represent the main compounds found in the urine. Faecal excretion corresponds mainly to the non-absorbed fraction of the drug.

中文翻译：

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D-青霉胺的临床药代动力学。

青霉胺以2种立体异构体的形式存在，但仅D异构体可用于治疗。它的化学反应性来自其官能团，其中巯基似乎是最重要的。由于青霉素胺的不稳定性，存在具有硫醇功能的内源性化合物以及其发生的各种化学形式（即还原的游离青霉素胺，与蛋白质结合的青霉素胺和内部（PSSP）和混合（PSSC）二硫化物。最早的测定方法（比色法，同位素方法，气相色谱法）既不灵敏也不特异。具有电化学检测功能的高效液相色谱法导致了对D-青霉胺的更特异性测定，可以根据衍生化反应或硫醇官能团的电氧化进行检测。使用双电极检测器（Au / Hg），可以直接检测二硫化物。D-青霉胺在肠道中迅速但不完全吸收（40％至70％），个体间差异很大。食物，抗酸剂，尤其是铁会减少药物的吸收。在吸收不良状态的患者中，其生物利​​用度也显着降低。血浆最高浓度出现在摄入后1至3小时，与剂量无关，口服250 mg后约为1至2 mg / L。一些研究者报道血浆中出现双峰，这可能不是由于肝肠循环所致。然后，血浆中的浓度迅速下降，通常遵循双相曲线。如果停止长期治疗，有一个缓慢的消除阶段，持续了4至6天，这表明存在一个“深层隔室”或“可逆性结合到组织的药物的缓慢池”，尤其是皮肤。这可以解释其治疗效果的持久性以及在治疗停止后发生不良副作用的原因。在长期治疗期间，个体之间的血浆浓度变化很大。它们似乎与类风湿关节炎患者的D-青霉胺的活性或毒性无关。血浆D-青霉胺的80％以上与蛋白质（特别是白蛋白）结合。其余主要为游离还原形式或为二硫化物。仅有一小部分剂量在肝脏中代谢为S-甲基-D-青霉胺。消除途径主要是肾脏。二硫化物代表尿液中发现的主要化合物。粪便排泄主要对应于药物的未吸收部分。