In vivo study of the distribution, affinity for cartilage and metabolism of glycosaminoglycan polysulphate (GAGPS, Arteparon)

37 patients suffering from osteoarthritis and 10 arthritic patients received intramuscular (i.m.), partly also intraarticular (i.ac.) injections of GAGPS; whereupon pharmacokinetics in serum, synovial fluid, urine, and cartilage were investigated. Cartilage was obtained during endoprosthetic hip surgery. The concentrations were determined by radiochemistry, partly after gel chromatography and electrophoresis respectively. Serum levels in patients with osteoarthritis after i.m. administration of 50 mg were 0.55 microgram/ml 3 hrs later, and 0.11 microgram/ml 24 hrs later. Patients with arthritis showed similar serum levels which were slightly higher after i.ac. injection, and which rose proportionally when the dosage was increased to 125 mg. With the arthritic patients, also the concentrations in the synovium were comparable, in the cases with osteoarthritis concentrations were slightly higher, which in both cases suggests that the synovial membrane is promptly penetrated. However, the concentrations in cartilage following a dosage of 50 mg within 24 hours rose as high as 1.45 micrograms/g which corresponds roughly to three times the serum level 3 hours after application. According to biochemical data, injections of 1 to 2 micrograms/ml should yield chondroprotective effects. Hitherto therapy has relied mainly on i.ac. injections; it may now be expanded by the i.m. route of administration. GAGPS was bound to serum proteins, in the synovia, however, it was found unbound. The main portion of the compound excreted via urine within 12 hrs (30 to 40 percent) was mainly unaltered; later, a partial degradation of the chain length and of the degree of sulfation was observed. Animal experiments on rats showed an increased affinity of GAGPS to inflamed tissues (Freund's adjuvant, carageenan edema).