Absorption, Distribution, Metabolism and Excretion of Glucosamine Sulfate
Absorption, Distribution, Metabolism and Excretion of Glucosamine Sulfate
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DOI：
10.1055/s-0031-1300105
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发表时间：
2001-09
期刊：
影响因子：
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通讯作者：
I. Setnikar;L. Rovati
中科院分区：
文献类型：
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作者：
I. Setnikar;L. Rovati
本文综述了晶体硫酸氨基葡萄糖（CGS）对葡萄糖胺（Gl）在人体和动物体内的吸收、分布、代谢和排泄（ADME）的相关文献。在人体中，单次静脉注射1005 mg CGS （628 mg Gl）后，母体Gl从血浆中消失，表观半衰期为1.11小时。用502 mg CGS给药的均匀14C标记Gl （14C-Gl）的研究表明，Gl的消失是由于与血浆球蛋白的结合，其滞后时间为0.45小时，速率为0.26 h−1。放射性在10 h后达到峰值，在95 h的1/2后消失。单次静脉注射502 mg CGS后，120 h的尿排泄量占给药剂量的29%。在大鼠和狗身上得到了一致的结果，放射性迅速出现在肝脏、肾脏和其他组织中，包括关节软骨。人静脉注射1005mg CGS后，用离子交换色谱法测定24 h尿中Gl的排泄量为给药量的38%，主要发生在给药后的前8 h。用14C-Gl示踪CGS得到了类似的结果。用14C-Gl追踪CGS的大鼠和狗的尿排泄结果一致。粪便中放射性物质的排泄量很少。在给药后的144小时内，大鼠测量到的14CO2与过期空气的放射性消除量为给药剂量的49%，其中16%发生在前6小时。CGS肌肉注射在人体内，单次肌肉注射502 mg 14C-G1追踪的CGS，其结果与静脉注射后的结果相似。口服CGS人体单次给药7.5 g CGS后，血浆中Gl低于离子交换色谱法定量限（3 μg/ml）。用14C-Gl示踪的314mg CGS单次剂量后，放射性出现在血浆球蛋白中，滞后时间为1.5 h，并以0.24 h−1的速率增加。在给药后第9小时达到峰值。58 h的t1/2消除放射性。以球蛋白结合放射性的auc评价的绝对口服生物利用度为44%。120小时的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%的差异可能是由于肝脏的首过效应。对14C-G1示踪剂量为126 ~ 3768 mg CGS的大鼠进行了研究，发现总放射性和去蛋白血浆中的auc以及剂量与Cmax之间存在线性关系。用离子交换色谱法测定，单次给药7.5 g CGS后24 h内亲本Gl的尿消除量为给药量的1.19%，主要发生在给药后的前8 h。连续给药1884 mg 7天后，尿中Gl的日排泄量从最初24 h的每日剂量的1.60%增加到最后24 h的每日剂量的2.22%，第2天后达到稳定状态。在重复给药过程中，尿液排泄处于稳定状态，从而得出结论：1884 CGS不论是糖衣片剂还是口服溶液，每天一次都具有生物等效性。在给药后的144小时内，大鼠的放射性消除量为给药剂量的82%，其中61%发生在前6小时。Gl与葡萄糖ADME的相互作用研究了在静脉注射或口服14C均匀标记的葡萄糖的大鼠中葡萄糖的ADME。葡萄糖在血浆中的动力学和组织分布与Gl完全不同，指出外源性葡萄糖为生化过程提供能量，而外源性Gl主要作为粘多糖和关节和骨骼生物聚合物的生物合成的底物。没有证据表明口服Gl与葡萄糖的ADME相互作用。
Summary 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-G1, 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 occured in the first 6 h. Intramuscular administration of CGS In man, a single intramuscular injection of 502 mg CGS traced with 14C-G1, 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 μg/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-G1, 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, occuring 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 bio-equivalent. 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.