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氨基葡萄糖在慢性给药时的血浆水平变化:可能是骨关节炎临床疗效不一致的原因。

Variation in Plasma Levels of Glucosamine With Chronic Dosing: A Possible Reason for Inconsistent Clinical Outcomes in Osteoarthritis.

机构信息

School of Pharmacy and Pharmacology, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.

School of Pharmacy and Pharmacology, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia; Faculty of Health, University of Canberra, Canberra, Australia.

出版信息

Clin Ther. 2020 Aug;42(8):e140-e149. doi: 10.1016/j.clinthera.2020.06.009. Epub 2020 Jul 24.

DOI:10.1016/j.clinthera.2020.06.009
PMID:32713600
Abstract

PURPOSE

Glucosamine is widely used by patients with osteoarthritis (OA) to provide symptomatic relief and to delay disease progression. However, clinical studies have reported inconsistent clinical outcomes. The current study hypothesized that the reported inconsistent clinical results could be, in part, due to variable bioavailability and elimination of glucosamine. This study therefore aimed to determine steady-state minimum plasma concentrations (C) of glucosamine to examine the variability among patients taking the supplement.

METHODS

Patients with OA who had been taking glucosamine for at least 1 week were recruited. Patients' blood samples were collected 24 h after the ingestion of the previous dose to determine Observed C and after a 5-day washout period to determine the endogenous glucosamine levels (GlcN). The Actual C was calculated by using the following equation: Actual C = Observed C - GlcN. The glucosamine plasma concentrations were determined by using a previously developed HPLC method.

FINDINGS

Ninety-one participants (age range, 42-89 years; mean [SD] age, 68.2 [7.6] years) were recruited (70% females). There was substantial (106-fold) variation, with a 45% coefficient of variation, between the Actual C levels (3-320 ng/mL) in participants. No significant association of Actual C was observed with various dose- and patient-related variables.

IMPLICATIONS

The observed high variability in steady-state plasma concentrations indicates substantial inter-patient differences in the absorption and elimination of glucosamine, which could be a cause for inconsistent clinical outcomes in patients with OA.

摘要

目的

氨基葡萄糖被广泛应用于骨关节炎(OA)患者,以提供症状缓解并延缓疾病进展。然而,临床研究报告的临床结果并不一致。本研究假设,报告的不一致的临床结果可能部分归因于氨基葡萄糖的生物利用度和消除的可变性。因此,本研究旨在确定氨基葡萄糖的稳态最小血浆浓度(C),以检查服用该补充剂的患者之间的变异性。

方法

招募了至少服用氨基葡萄糖 1 周的 OA 患者。患者在服用前一剂 24 小时后采集血样,以确定观察到的 C,并在 5 天洗脱期后确定内源性氨基葡萄糖水平(GlcN)。实际 C 通过以下公式计算:实际 C=观察到的 C-GlcN。使用先前开发的 HPLC 方法测定氨基葡萄糖的血浆浓度。

发现

招募了 91 名参与者(年龄范围 42-89 岁;平均[SD]年龄 68.2[7.6]岁)(70%为女性)。参与者的实际 C 水平(3-320ng/mL)存在很大(106 倍)差异,变异系数为 45%。实际 C 与各种剂量和患者相关变量之间没有显著相关性。

结论

稳态血浆浓度观察到的高变异性表明氨基葡萄糖的吸收和消除存在显著的个体间差异,这可能是 OA 患者临床结果不一致的原因。

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