Komatsu S, Iwata H, Nabeshima T
Department of Medical Information Development, Hoechst Marion Roussel Ltd., Tokyo, Japan.
Arzneimittelforschung. 1999 May;49(5):427-33. doi: 10.1055/s-0031-1300438.
The pharmacokinetics of hyaluronan (HA) (CAS 9004-61-9) was measured after intra-articular (i.a.) injection of 1 mg/kg of 14C-glucose-labelled HA (14C-HA) (i.e. 2,000 kDa) into the knee joint cavity of rabbits. The movement of HA from the cavity into the systemic circulation was assessed by measuring its concentration in blood and its residue in the cavity. I.a. HA moved into, and disappeared from, the bloodstream at a first-order rate. Synovial fluid, synovial membrane and articular cartilage specimens were taken 24 and 72 h post-injection, and the molecular weight (MW) of HA fractions were measured by using gel filtration chromatography (GFC) using radioactive fractions of known molecular sizes (i.e. 2,000 kDa, 300 kDa and 50 kDa). The radioactivity distribution of synovial fluid had a peak at a 2,000 kDa-equivalent fraction at both 24 and 72 h post-injection, while synovial membrane had a peak at a 300 kDa-equivalent fraction 24 h post-injection and at a 50 kDa-equivalent fraction 72 h post-injection. The radioactivity distribution pattern of articular cartilage showed peaks corresponding to 2,000-300 kDa 24 h post-injection and to 50 kDa 72 h post-injection. The in vivo re-utilisation of i.a. HA was investigated by assessing radioactivity in the acid-soluble, lipid and protein fractions of plasma, blood cells and liver 72 h post-injection. Results show that HA was broken down into C1 units (carbon cycle) before being re-used as an in vivo constituent in the body.
将1毫克/千克的14C-葡萄糖标记的透明质酸（14C-HA）（即2000 kDa）关节腔内注射到兔膝关节腔后，测定了透明质酸（HA）（CAS 9004-61-9）的药代动力学。通过测量其在血液中的浓度及其在腔内的残留量来评估HA从腔内向体循环的移动。关节腔内注射的HA以一级速率进入血流并从血流中消失。在注射后24小时和72小时采集滑膜液、滑膜和关节软骨标本，并使用凝胶过滤色谱法（GFC），利用已知分子大小（即2000 kDa、300 kDa和50 kDa）的放射性级分测量HA级分的分子量（MW）。滑膜液的放射性分布在注射后24小时和72小时时在相当于2000 kDa的级分处有一个峰值，而滑膜在注射后24小时时在相当于300 kDa的级分处有一个峰值，在注射后72小时时在相当于50 kDa的级分处有一个峰值。关节软骨的放射性分布模式在注射后24小时时显示对应于2000 - 300 kDa的峰值，在注射后72小时时显示对应于50 kDa的峰值。通过评估注射后72小时时血浆、血细胞和肝脏的酸溶性、脂质和蛋白质级分中的放射性来研究关节腔内注射的HA在体内的再利用情况。结果表明，HA在被重新用作体内成分之前先分解为C1单位（碳循环）。
