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口服放射性标记的D-青霉胺后的药代动力学研究

[Pharmacokinetic studies after oral application of radioactively labelled D-penicillamine].

作者信息

Patzschke K, Wegner L, Kaller H, Horster F A

出版信息

Z Rheumatol. 1977 Mar-Apr;36(3-4):96-105.

PMID:871071
Abstract

14C-labelled D-penicillamine was given orally to healthy test subjects in different dosages. The time course of serum activity was followed up to 5 weeks and the urinary activity was measured for 4 days. The obtained results equalled the sum of active substance and its 14C-labelled biotransformation products. The maximal serum concentration appeared about 2 hours after ingestion, the obtained concentrations being proportional to the dosis. Thereafter the concentration declined first relatively fast, then increasingly slower. From the 4th day after ingestion the half time of elimination was 8 days. The urinary excretion was dose dependent; the urinary concentration increasing with higher dosage. The later long half time of elimination corresponded to disappearance from the blood of the portion of the drug firmly getting attached to collagen and elastic tissue structures. The several weeks latency of onset of antirheumatic effect may be due to the fact that the portion of the drug getting attached to connective tissue accumulates slowly.

摘要

将不同剂量的14C标记的D-青霉胺口服给予健康受试对象。对血清活性的时间进程进行了长达5周的跟踪,并对4天内的尿液活性进行了测量。所获得的结果等于活性物质及其14C标记的生物转化产物的总和。最大血清浓度在摄入后约2小时出现,所获得的浓度与剂量成正比。此后,浓度首先相对快速下降,然后下降速度越来越慢。从摄入后第4天起,消除半衰期为8天。尿排泄呈剂量依赖性;尿浓度随剂量增加而升高。后期较长的消除半衰期对应于牢固附着在胶原蛋白和弹性组织结构上的那部分药物从血液中的消失。抗风湿作用起效的数周潜伏期可能是由于附着在结缔组织上的那部分药物积累缓慢。

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