In controlled trials, glucosamine and its combination with chondroitin have not been linked to serum enzyme elevations or to instances of clinically apparent liver injury. In addition, cases of clinically apparent liver injury have not been reported from prospective trials. Recently, several cases reports and small series of clinically apprent liver injury attributed to glucosamine (with or without chondroitin) have been published, but the relationship of glucosamine itself as opposed to other herbals in the implicated products or to potential contaminants, remains unclear and several cases were considered only "possibly" related to glucosamine. The time to onset is usually 1 to 4 weeks after starting the preparation and the pattern of injury is typically hepatocellular or mixed. At least one instance of acute liver failure has been reported. Immunoallergic features (rash, fever, eosinophilia) can occur, but are usually not prominent. Most patients were reported to recover within 4 to 8 weeks of stopping. There have not been instances of rechallenge with glucosamine, and the purity and concentration of glucosamine in the products used have not been reported.
◉ Summary of Use during Lactation:Glucosamine is an amino-monosaccharide that is either derived from shellfish or synthetically produced. Glucosamine sulfate has no specific lactation-related uses. It is most commonly used to treat osteoarthritis. A glucosamine derivative, N-acetylglucosamine, is a normal component of human breastmilk. Glucosamine sulfate is well tolerated with occasional gastrointestinal discomfort (e.g., diarrhea, heartburn, nausea, vomiting) reported. Although no studies exist on the use of glucosamine sulfate during breastfeeding, its use by a nursing mother is unlikely to adversely affect the breastfed infant.
Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用带气囊的面罩进行正压通气技术可能有益。考虑使用药物治疗肺水肿...。对于严重的支气管痉挛，可以考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注5%葡萄糖水（D5W）/SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%盐水（NS）或乳酸林格液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象...。使用地西泮或劳拉西泮治疗癫痫...。使用丙美卡因氢氯化物协助眼部冲洗...。/Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
/LABORATORY ANIMALS: Acute Exposure/ Glucosamine (Glmn), a product of glucose metabolism via the hexosamine pathway, causes insulin resistance in isolated adipocytes by impairing insulin-induced GLUT 4 glucose transporter translocation to the plasma membrane. /It was/ hypothesized that Glmn causes insulin resistance in vivo by a similar mechanism in skeletal muscle. Euglycemic hyperinsulinemic clamps (12 mU/kg/min + 3H-3-glucose) /were performed/ in awake male Sprague-Dawley rats with and without Glmn infusion at rates ranging from 0.1 to 6.5 mg/kg/min. After 4h of euglycemic clamping, hindquarter muscles were quick-frozen and homogenized, and membranes were subfractionated by differential centrifugation and separated on a discontinuous sucrose gradient (25, 30, and 35% sucrose). Membrane proteins were solubilized and immunoblotted for GLUT 4. With Glmn, glucose uptake (GU) was maximally reduced by 33 +/- 1%, P < 0.001. The apparent Glmn dose to reduce maximal GU by 50% was 0.1 mg/kg/min or 1/70th the rate of GU on a molar basis. Control galactosamine and mannosamine infusions had no effect on GU. Relative to baseline, insulin caused a 2.6-fold increase in GLUT 4 in the 25% membrane fraction (f), P < 0.01, and a 40% reduction in the 35%f, P < 0.05, but had no effect on GLUT 4 in the 30% f, P= NS. Addition of Glmn to insulin caused a 41% reduction of GLUT 4 in the 25%f, P < 0.05, a 29% fall in the 30%f, and prevented the reduction of GLUT 4 in the 35% f. The 30%f membranes were subjected to a second separation with a 27 and 30% sucrose gradient. Insulin mobilized GLUT 4 away from the 30%f, P < 0.05, but not the 27% f. In contrast, Glmn reduced GLUT 4 in the 27%f, P < 0.05, but not the 30%f. Thus Glmn appears to alter translocation of an insulin-insensitive GLUT 4 pool. Coinfusion of Glmn did not alter enrichment of the sarcolemmal markers 5'-nucleotidase, Na+/K+ATPase, and phospholemman in either 25, 30, or 35% f. Thus Glmn completely blocked movement of Glut 4 induced by insulin. Glmn is a potent inducer of insulin resistance in vivo by causing (at least in part) a defect intrinsic to GLUT 4 translocation and/or trafficking. These data support a potential role for Glmn to cause glucose-induced insulin resistance (glucose toxicity).
In a pharmacokinetic study, glucosamine was 88.7% absorption by the gastrointestinal tract. Absolute oral bioavailability was 44%, likely due to the hepatic first-pass effect. In a pharmacokinetic study of 12 healthy adults receiving oral crystalline glucosamine, plasma levels increased up to 30 times the baseline levels and Cmax was 10 microM with a 1,500 mg once-daily dose. Tmax was about 3 hours. AUC was 20,216 ± 5021 after a 15,000 mg dose.
Fecal excretion of glucosamine in a pharmacokinetic study was 11.3% within 120 hours after administration. Urinary elimination was found to be 1.19% within the first 8 hours post-administration.
Results of a pharmacokinetic study of 12 healthy volunteers receiving three daily consecutive oral administrations of glucosamine sulfate soluble powder demonstrated glucosamine distribution to extravascular compartments. Human pharmacokinetic data for glucosamine is limited in the literature, however, a large animal model study of horses revealed a mean apparent volume of distribution of 15.4 L/kg. Concentrations of glucosamine ranged from 9-15 microM after an intravenous dose, and 0.3-0.7 microM after nasogastric dosing. These concentrations remained in the range of 0.1-0.7 microM in the majority of horses 12 hours after dosing, suggesting effectiveness of a once-daily dose. In rats and dogs, radioactivity from a C-14 labeled dose of glucosamine is detected in the liver, kidneys, articular cartilage, and other areas.
Information on the absorption and serum pharmacokinetics for dietary glucosamine is very limited, and in some case, the available data are contradictory. For example, in one series of studies, (14)C-glucosamine was given orally to rats, dogs, and humans, and in all cases, the radiolabel was described as "efficiently" absorbed, reaching a plasma peak after about 4 hours. A high percentage of the radiolabel (about 35%) was excreted in the urine, and a similar amount was last in expired air. On the other hand, the laboratory that conducted this experiment was unable to detect chemical amounts of glucosamine in human serum after a single oral dose at 100 mg/kg (five times the clinical dose) using a chromatographic assay with a limit of detection of about 14 uM. This suggests that the bioavailable glucosamine in human serum after the normal recommended dosage (20 mg/kg) is well below 10 uM.
About 90% of glucosamine administered orally as a glucosamine salt get absorbed from the small intestine, and from there it is transported via the portal circulation to the liver. It appears that a significant fraction of the ingested glucosamine is catabolized by first-pass metabolism in the liver. Free glucosamine is not detected in the serum after oral intake, and it si not presently known how much of an ingested dose is taken up in the joints in humans. Some uptake in the articular cartilage is seen in animal studies.
