[Pharmacokinetic studies following administration of 14 C-D-penicillamine to rats]

14C-Labelled D-penicillamine [D-(--)-alpha-amino-beta-mercapto-isovaleric acid; Trolovol] was administered to rats in doses of 10 to 50 mg/kg body weight orally or i.v. A dose of 0.25 mg per rat was used for intra-articular injection (knee joint). 4 h after a single i.v. administration about 30% of the given amount were detected in the animal. This amount of activity was located predominantly in skin and connective tissues and was eliminated very slowly. 2 days after administration 20 (i.v.) or 10 (p.o.)%, resp., of the radioactivity administered were found in the animal, in any case half of it in the skin. In comparison to the skin and the connective tissues, the parenchymatous organs and the central nervous system showed distinctly lower concentrations. The activity is eliminated mainly with the urine: 80 (i.v.) or 50 (p.o.)%, resp., of the administered activity were eliminated renally within 48 h. 90% of it were excreted within 6 (i.v.) or 7 (p.o.) h, resp., after administration. Less than 2 (i.v.) and approx. 40 (p.o.)%, resp., of the given activity were found in the faeces collected for 2 days. The extent of gastrointestinal absorption was about 2/3 of the dose administered. Up to 24 h after the three modes of administration distinctly detectable concentrations were to be located in the lig. patellae of the knee joints, somewhat lower values in the ligaments between the articular cartilages. Studies carried out on rats in parallel with an arthritis experimentally induced (secondary phase, after injection of Freund's adjuvant) demonstrated the same activity distribution compared with the pattern which was obtained on healthy rats.