Setnikar I, Rovati L C
Scientific Department, Rotta Research Laboratorium, Monza, Italy.
Arzneimittelforschung. 2001 Sep;51(9):699-725. doi: 10.1055/s-0031-1300105.
This article reviews the literature related to the absorption, distribution, metabolism and excretion (ADME) of glucosamine (Gl) in man and in animals after administration of crystalline glucosamine sulfate (CGS). Intravenous administration of CGS In man, after single bolus intravenous (i.v.) injection of 1005 mg CGS (628 mg Gl), the parent Gl disappears from plasma with an apparent half life of 1.11 h. Investigations with uniformly 14C labeled Gl (14C-Gl) administered with 502 mg CGS indicate that the disappearance of Gl is due to an incorporation into the plasma globulins that occurs with a lag time of 0.45 h and a rate of 0.26 h-1. The radioactivity reaches a peak after 10 h and is eliminated with a t1/2 of 95 h. After single i.v. doses of 502 mg CGS traced with 14C-Gl, the urinary excretion in 120 h accounted for 29% of the administered dose. Consistent results are obtained in rat and dogs, in which radioactivity rapidly appears in liver, kidneys and other tissues, including the articular cartilage. In man, after i.v. bolus injection of 1005 mg CGS, the urinary excretion in 24 h of Gl determined with ion exchange chromatography was 38% of the administered dose, mostly in the first 8 h after administration. Similar results were obtained tracing CGS with 14C-Gl. Consistent results of urinary excretion were obtained in rats and dogs tracing CGS with 14C-Gl. The excretion of radioactivity in feces was small. The elimination of radioactivity with the expired air as 14CO2 measured in rats amounted to 49% of the administered dose in the 144 h following the administration, 16% of which occurred in the first 6 h. Intramuscular administration of CGS In man, a single intramuscular injection of 502 mg CGS traced with 14C-Gl, gave results similar to those after i.v. administration. Oral administration of CGS In man, after a single dose of 7.5 g CGS, Gl in plasma was below the limit of quantitation (3 micrograms/ml) of the ion exchange chromatography method. After a single dose of 314 mg CGS traced with 14C-Gl, radioactivity appeared incorporated in plasma globulins with a lag time of 1.5 h and increasing with a rate of 0.24 h-1. The peak was reached at the 9th h after administration. The radioactivity then was eliminated with a t1/2 of 58 h. The absolute oral bioavailability evaluated on the AUCs of the globulin-incorporated radioactivity was 44%. The fecal excretion in 120 h was 11.3% of the administered dose showing that at least 88.7% of the administered dose was absorbed through the gastrointestinal tract. The difference of 45% is probably due to a hepatic first-pass effect. Investigated in the rat with doses from 126 to 3768 mg CGS traced with 14C-Gl, a linear relationship was found with the AUCs as well as between doses and the Cmax of radioactivity in total and in deproteinized plasma. The urinary elimination in man of the parent Gl in 24 h determined with ion exchange chromatography after a single dose of 7.5 g of CGS was 1.19% of the administered dose, occurring mostly in the first 8 h after administration. After administration of 1884 mg repeated for 7 days the daily urinary excretion of Gl increased from 1.60% of the daily dose during the first 24 h to 2.22% of the daily dose in the last 24 h. The steady state was reached after the second day. The urinary excretion at steady state during repeated administration allowed to conclude that daily 1884 CGS administered either t.i.d. in sugar coated tablets or once a day in oral solution were bioequivalent. The elimination of radioactivity with the expired as 14CO2 measured in rats was 82% of the administered dose in the 144 h following the administration, 61% of which occur in the first 6 h. Interaction of Gl with the ADME of glucose The ADME of glucose was investigated in the rat administering i.v. or orally 14C uniformly labeled glucose. The kinetic in plasma and the tissue distribution of glucose differed totally from those of Gl, pointing out that exogenous glucose provides the energy for biochemical processes, whereas exogenous Gl acts mainly as substrate for the biosynthesis of mucopolysaccharides and of biopolymers of the articulations and bones. There was no evidence of interaction by Gl orally administered with the ADME of glucose.
本文综述了有关人及动物在给予结晶硫酸葡萄糖胺（CGS）后，葡萄糖胺（Gl）的吸收、分布、代谢及排泄（ADME）的相关文献。
人体静脉注射CGS：在单次静脉推注1005mg CGS（628mg Gl）后，母体Gl从血浆中消失，表观半衰期为1.11小时。用502mg CGS给予均匀标记的14C - Gl进行研究表明，Gl的消失是由于其掺入血浆球蛋白，这一过程的延迟时间为0.45小时，速率为0.26h - 1。放射性在10小时后达到峰值，消除半衰期为95小时。单次静脉注射502mg CGS并用14C - Gl追踪，120小时内尿排泄量占给药剂量的29%。在大鼠和狗身上也得到了一致的结果，放射性迅速出现在肝脏、肾脏和其他组织，包括关节软骨中。在人体中，静脉推注1005mg CGS后，用离子交换色谱法测定24小时内Gl的尿排泄量为给药剂量的38%，大部分在给药后的前8小时内。用14C - Gl追踪CGS也得到了类似的结果。在大鼠和狗身上用14C - Gl追踪CGS，尿排泄结果一致。粪便中的放射性排泄量很少。在大鼠中测定，给药后144小时内通过呼出空气以14CO2形式排出的放射性占给药剂量的49%，其中16%发生在最初6小时内。
人体肌肉注射CGS：单次肌肉注射502mg CGS并用14C - Gl追踪，结果与静脉注射后相似。
人体口服CGS：单次给予7.5g CGS后，血浆中的Gl低于离子交换色谱法的定量限（3μg/ml）。单次给予314mg CGS并用14C - Gl追踪后，放射性在1.5小时的延迟时间后开始掺入血浆球蛋白，并以0.24h - 1的速率增加。给药后第9小时达到峰值。然后放射性以58小时的半衰期消除。根据掺入球蛋白的放射性的AUC评估的绝对口服生物利用度为44%。120小时内粪便排泄量为给药剂量的11.3%，表明至少88.7%的给药剂量通过胃肠道吸收。45%的差异可能归因于肝脏首过效应。在大鼠中用14C - Gl追踪给予126至3768mg CGS的剂量，发现AUC以及总血浆和脱蛋白血浆中放射性的剂量与Cmax之间存在线性关系。单次给予7.5g CGS后，用离子交换色谱法测定24小时内母体Gl在人体中的尿排泄量为给药剂量的1.19%，主要发生在给药后的前8小时内。给予1884mg并重复7天，Gl的每日尿排泄量从最初24小时内每日剂量的1.60%增加到最后24小时内每日剂量的2.22%。第二天达到稳态。重复给药期间稳态时的尿排泄情况表明，每日给予1884mg CGS，无论是糖衣片每日三次还是口服溶液每日一次，都是生物等效的。在大鼠中测定，给药后144小时内通过呼出空气以14CO2形式排出的放射性占给药剂量的82%，其中61%发生在最初6小时内。
Gl与葡萄糖ADME的相互作用：在大鼠中通过静脉注射或口服均匀标记的14C葡萄糖来研究葡萄糖的ADME。葡萄糖在血浆中的动力学和组织分布与Gl完全不同，这表明外源性葡萄糖为生化过程提供能量，而外源性Gl主要作为关节和骨骼中粘多糖及生物聚合物生物合成的底物。没有证据表明口服Gl与葡萄糖的ADME之间存在相互作用。
