Variation in the pharmacokinetics of glucosamine in healthy individuals.

OBJECTIVES: Clinical trial data for the efficacy of glucosamine in OA are conflicting. Reportedly, Rotta-manufactured glucosamine products are more likely to be effective, and a possible explanation is greater bioavailability than other brands. Specifically, the aim was to compare the steady-state pharmacokinetics of Rotta- and non-Rotta-manufactured glucosamine products in healthy volunteers and examine the interindividual variability. METHODS: In a crossover design, healthy adult participants ingested 1500 mg/day of a Rotta (DONA powder sachets; imported by Mylan Health, Carole Park, QLD, Australia) and a non-Rotta (glucosamine sulphate 1500 mg one-a-day tablet; Blackmores, Warriewood, NSW, Australia) glucosamine product/brand individually for 6 days. Blood samples were collected immediately before and for 12 h after the ingestion of the last dose of each brand and analysed to determine plasma levels of glucosamine. The pharmacokinetic parameters at steady state [including the minimum (Css min) and maximum (Css max) plasma concentration of glucosamine, time to reach Css max post-dosing (Tss max) and area under the plasma concentration vs time curve (AUCss 0-12)] for each brand were calculated and statistically compared. RESULTS: Fourteen participants [mean age 35.5 years (s.d. 8.8)] were recruited (64.2% males). No significant differences were observed in the pharmacokinetic parameters between the two brands. However, for both brands, the coefficient of variation for Css min, Tss max and AUCss 0-12 exceeded 20%, indicating considerable differences in the parameters between participants. No significant association of the pharmacokinetic parameters was observed with various dosing- and participant-related variables. CONCLUSION: Substantial interindividual differences in the absorption and elimination of glucosamine could be a cause of variable clinical outcomes in OA. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ACTRN12618000699268p.aspx), number ACTRN12618000699268p.

WSe2crystals on paper: flexible, large area and broadband photodetectors.

The paper-based photodetector has recently captivated a great deal of attention in various opto-electronics applications because of facile, cost effective and green synthesis. Two-dimensional transition metal dichalcogenides materials are promising for photodetection under the broad spectral range. In this work, we have fabricated paper-based device by rubbing the tungsten di-selenide (WSe2) crystals on paper substrate. Low-cost, facile and green synthesis technique was employed to make a high-performance paper-based WSe2photodetector. Paper-based photodetector was fabricated via non-toxic simply rubbing process of WSe2nanosheets on low-cost bio-degradable paper. The photodetector shows good responsivity of 72.5 µA W-1and detectivity at around 2.4 × 107Jones at very low bias (1.0 V) at wavelength of 780 nm, respectively. Due to good photo-absorption strength, photodetector exhibits excellent photo-response over wide wavelength range from visible to near infrared. This device also shows very good flexibility with a stable photo-response. This device shows a general and reliable study for the design of photodetectors that is eco-friendly and cost-effective. Overall studied results of the fabricated device indicate that they have the ability to be used in large-scale preparation of the device.

Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators.

Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.

Physicochemical stability of extemporaneously prepared clonidine solutions for use in neonatal abstinence syndrome.

WHAT IS KNOWN AND OBJECTIVE: Extemporaneously prepared clonidine admixture is increasingly used for the management of neonatal abstinence syndrome. However, its stability beyond 15 minutes at room temperature is currently unknown. Therefore, healthcare professionals must prepare clonidine admixtures multiple times a day while the treatment is indicated, resulting in subsequent limitations and problems. The aim of this study was to investigate the physicochemical stability of clonidine in commonly used pharmaceutical diluents at clinically relevant concentrations and temperatures. METHODS: Glass bottles (n = 18) and plastic syringes (n = 18) containing 0.5 and 5 µg/mL of clonidine in either 5% glucose, 10% glucose or 0.9% normal saline were prepared and stored at 4°C for 7 days and at 35°C for 24 hours, respectively. Aliquots were withdrawn at predefined time points and analysed for the concentration of clonidine, changes in pH and colour, and particle content. RESULTS AND DISCUSSION: No evidence of particle formation, or colour or pH change was observed throughout the study period. Clonidine retained more than 98% of its initial concentration when stored in the tested diluents at 4°C for 7 days and at 35°C for 24 hours. WHAT IS NEW AND CONCLUSION: Our findings will allow healthcare professionals to prepare weekly dose of clonidine in glass bottles for storage in a refrigerator. The daily required dose of clonidine can be drawn aseptically from the glass bottle each day and stored in a plastic syringe at room temperature. Clonidine present in a plastic syringe can be administered via the nasogastric route 4-6 times a day. This practice would not only save nursing time and avoid delays in the timely administration of clonidine, but also reduce the risk of potential medication errors as well as preparation-associated costs.

Completeness and Legibility of Handwritten Prescriptions in Sana'a, Yemen.

OBJECTIVE: The aim of this study was to investigate the completeness and legibility of prescriptions dispensed in community pharmacies located in Sana'a, Yemen. MATERIALS AND METHODS: A cross-sectional study was conducted at 23 randomly selected community pharmacies throughout the capital city of Sana'a, Yemen, from May 2015 to January 2016. A total of 2,178 prescriptions were analyzed for the essential elements of a complete prescription using a validated checklist. RESULTS: Of the 2,178 prescriptions, 19 (0.87%) were considered to be of good quality. The remaining 2,159 (99.12%) were considered as being of very poor quality. Writing errors relating to patients and prescribed medications were the most common errors. CONCLUSION: In this study, the quality of prescription writing was found to be very poor. Hence, continuous professional development programs are recommended to improve the quality of prescription writing among physicians. Future studies in other cities and investigation of the impact of continuous educational programs on the quality of prescription writing are strongly recommended.

Redefining Approaches to Asthma: Bridging the Gap Between Heparin and Its Anti-inflammatory Activities.

Heparin is widely used as an anticoagulant. Currently, this macromolecule is at the forefront in the field of glycobiology because of the recognition of its therapeutic potential in a wide range of medical conditions including inflammation. Heparin is composed of anticoagulant and non-anticoagulant molecules. A large body of evidence suggests that the anti-inflammatory activities of heparin are attributed to its non-anticoagulant molecules and are therefore independent to its anticoagulant effect. However, the potential therapeutic use of heparin in inflammatory conditions is hindered by the presence of anticoagulant molecules causing the risk of bleeding. Therefore, there is an emerging interest in identifying non-anticoagulant molecules of heparin responsible for the anti-inflammatory effects of the parent molecule. The present editorial commentary focuses on the non-anticoagulant applications of heparin for the management of asthma. The commentary concisely describes the plausible mechanisms of action of heparin involved in the therapy of asthma. It also discusses various approaches that are utilised for the development of novel non-anticoagulant analogues of heparin that possess the potent anti-asthmatic activity of the parent molecule but are devoid of anticoagulant effect. We also briefly outline potential future approaches for the use of this molecule as an effective anti-inflammatory agent.

Fabrication of a wearable and foldable photodetector based on a WSe2-MXene 2D-2D heterostructure using a scalable handprint technique.

Several studies on semiconductor material-based single-band, high-performance photosensitive, and chemically stable photodetectors are available; however, the lack of broad spectral response, device flexibility, and biodegradability prevents them from being used in wearable and flexible electronics. Apart from that, the selection of the device fabrication technique is a very crucial factor nowadays in terms of equipment utilization and environmental friendliness. This report presents a study demonstrating a straightforward solvent- and equipment-free handprint technique for the fabrication of WSe2-Ti3C2TX flexible, biodegradable, robust, and broadband (Vis-NIR) photodetectors. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), UV-visible spectroscopy, and X-ray photoelectron spectroscopy (XPS) confirm the formation of a WSe2-Ti3C2TX film. The WSe2-Ti3C2TX van der Waals heterostructure plays a key role in enhancing the optoelectrical properties. The as-prepared photodetector exhibits efficient broadband response with a photoresponsivity and a detectivity of 0.3 mA W-1 and 6.8 × 1010 Jones, respectively, under NIR (780 nm) irradiation (1.0 V bias). Under various pressure and temperature conditions, the device's flexibility and durability were tested. The biodegradable photodetector prepared through the solvent- and equipment-free handprint technique has the potential to attract significant interest in wearable and flexible electronics in the future.

Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

ABSTRACT: Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace (http://painface.net) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.

Ion exchange chromatographic separation and isolation of oligosaccharides of intact low-molecular-weight heparin for the determination of their anticoagulant and anti-inflammatory properties.

It is well known that enoxaparin, a widely used anticoagulant and low-molecular-weight heparin containing a large number of oligosaccharides, possesses anti-inflammatory activity. Whilst enoxaparin has shown promising results in various inflammatory disorders, some of its oligosaccharides have anti-inflammatory properties and others increase the risk of bleeding due to their anticoagulant effects. The aim of this study was to develop an effective ion exchange chromatographic (IC) technique which allows the separation, isolation and, consequently, the identification of different oligosaccharides of enoxaparin with or without anticoagulant activity. The developed method utilises a semi-preparative CarboPac PA100 (9 × 250 mm) ion exchange column with sodium chloride gradient elution and UV detection at 232 nm. The method successfully resolved enoxaparin into more than 30 different peaks. IC-derived oligosaccharides with high, moderate, low or no anticoagulant activity were identified using an anti-factor Xa assay. The anti-inflammatory activity of selected oligosaccharides was investigated using the Griess assay. Using this technique, the oligosaccharides of enoxaparin with low or no anticoagulant activity, whilst exhibiting significant anti-inflammatory activity, could be fractionated. This technique can provide a platform to identify the oligosaccharides which are devoid of significant anticoagulant activity and are responsible for the therapeutic effects of enoxaparin that have been observed in various inflammatory conditions.

Treatment and outcomes of peritonitis due to Rothia species in patients on peritoneal dialysis: A systematic review and multicentre registry analysis.

Peritoneal dialysis (PD)-associated peritonitis remains a severe complication of PD. Although peritonitis due to Rothia spp. is rare, the treatment recommendations and outcomes are uncertain. Our study aims to review (1) published literature on peritonitis caused by Rothia spp. and (2) reported cases of peritonitis due to Rothia spp. in patients on PD in Australia and New Zealand. A literature search of PubMed, Scopus, Embase and Google Scholar for articles published between January 1949 and February 2022 was conducted. To be eligible, articles had to describe antibiotic therapy and treatment outcomes in all PD patients for peritonitis caused by Rothia or Stomatococcus spp. Data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry of PD patients who developed peritonitis due to Rothia spp. between July 2011 and May 2020 were also reviewed. A total of 12 articles and 28 episodes were identified from the literature search and ANZDATA registry analysis, respectively. Over 60% of the peritonitis cases due to Rothia spp. were from the Rothia mucilaginosa species (8/12 and 17/28, respectively), while Rothia dentocariosa was the second most commonly identified species in both the literature search and the ANZDATA registry analysis (4/12 and 5/28, respectively). A majority 8 (66.7%) of the articles in the literature search employed a combination antibiotic regimen, while the remaining 4 (33.3%) used a single antibiotic regimen. In contrast, most of the episodes, 22 (78.6%) described in the ANZDATA registry analysis, employed a single antibiotic regimen, and only 6 (21.4%) episodes were treated with a combination antibiotic regimen. The duration of antibiotic therapy ranged from 2 to 3 weeks in the literature search, and 1 to 3 weeks in the ANZDATA registry. While no deaths within 30 days of developing peritonitis were reported, catheter removal was reported in three (25%) and two (7.1%) episodes in both the literature search and the ANZDATA registry analysis, respectively, of which the majority occurred in patients treated for ≤2 weeks. PD-associated peritonitis due to Rothia spp. is uncommon and associated with relatively good outcomes. Antibiotic treatment for 3 weeks is associated with better outcomes.

A Systematic Review and Meta-Analysis on the Therapeutic Efficacy of Heparin and Low Molecular Weight Heparins in Animal Studies of Traumatic Brain Injury.

The identification of effective pharmacotherapies for traumatic brain injury (TBI) remains a major challenge. Treatment with heparin and its derivatives is associated with neuroprotective effects after experimental TBI; however, the optimal dosage and method of administration, modes of action, and effects on hemorrhage remain unclear. Therefore, this review aimed to systematically evaluate, analyze, and summarize the available literature on the use of heparin and low molecular weight heparins (LMWHs) as treatment options for experimental TBI. We searched two online databases (PubMed and ISI Web of Science) to identify relevant studies. Data pertaining to TBI paradigm, animal subjects, drug administration, and all pathological and behavior outcomes were extracted. Eleven studies met our pre-specified inclusion criteria, and for outcomes with sufficient numbers, data from seven publications were analyzed in a weighted mean difference meta-analysis using a random-effects model. Study quality and risk of bias were also determined. Meta-analysis revealed that heparin and its derivatives decreased brain edema, leukocyte rolling, and vascular permeability, and improved neurological function. Further, treatment did not aggravate hemorrhage. These findings must be interpreted with caution, however, because they were determined from a limited number of studies with substantial heterogeneity. Also, overall study quality was low based on absences of data reporting, and potential publication bias was identified. Importantly, we found that there are insufficient data to evaluate the variables we had hoped to investigate. The beneficial effects of heparin and LMWHs, however, suggest that further pre-clinical studies are warranted.

Practice variations in antibiotic administration for the management of peritonitis in patients on automated peritoneal dialysis in Australia and New Zealand.

In the absence of guidelines on the management of peritoneal dialysis (PD)-associated peritonitis in patients on automated peritoneal dialysis (APD), variations in clinical practice potentially exist between PD units that could affect clinical outcomes. This study aimed to document the current practices of treating PD-associated peritonitis in patients on APD across Australia and New Zealand and the reasons for practice variations using a cross-sectional online survey. Of the 62 PD units, 34 medical leads (55%) responded to the survey. When treating APD-associated peritonitis, 21 units (62%) continued patients on APD and administered intraperitoneal (IP) antibiotics in manual daytime exchanges; of these, 17 (81%) considered allowing at least 6 h dwell time for adequate absorption of the IP antibiotics as an important reason for adding manual daytime exchange. Nine units (26%) temporarily switched patients from APD to continuous ambulatory peritoneal dialysis (CAPD); of these, five (55%) reported a lack of pharmacokinetic (PK) data for IP antibiotics in APD, four (44%) reported a shortage of APD-trained nursing staff to perform APD exchanges during hospitalisation and three (33%) reported inadequate time for absorption of IP antibiotics on APD as important reasons for their practice. Four units (12%) continued patients on APD and administered IP antibiotics during APD exchanges; of these, three (75%) believed that PK data available in CAPD could be extrapolated to APD. This study demonstrates wide variations in the management of APD-associated peritonitis in Australia and New Zealand; it points towards the lack of PK on antibiotics used to treat peritonitis as an important reason underpinning practice variations.

Quality of Glucosamine Products: Is it a Potential Reason for Inconsistent Clinical Outcomes in Osteoarthritis?

BACKGROUND: Clinical studies have reported inconsistent outcomes of glucosamine therapy in osteoarthritis patients. One possible reason could be the use of glucosamine products of varying quality. OBJECTIVE: Hence, this study aimed to assess the quality of glucosamine products marketed in Australia and India. This is the first study to investigate both the content and dissolution profiles of glucosamine products. METHOD: The content and dissolution analysis of Australian (n = 25 brands) and Indian (n = 21 brands) glucosamine products was performed according to the criteria specified in the United States Pharmacopoeia (USP). RESULTS: The quality analysis revealed that 16% and 18% of Australian brands, as well as 24% and 19% of Indian brands, did not fulfil the USP content and dissolution criteria, respectively. In approximately half of these cases, the glucosamine content was only slightly below (<3%) that specified by the USP and dissolution was achieved within 15 min after the duration specified by the USP. CONCLUSIONS: The majority of the brands did meet both the content and dissolution analysis criteria of the USP. The extent of deviation from the specified criteria for the other brands was probably insufficient to account for the significant variability in clinical effects. Hence, the study proposed that inter-patient pharmacokinetic variations in glucosamine could be another potential reason for inconsistent therapeutic effects.

Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review.

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

An Appraisal of the Current Scenario in Vaccine Research for COVID-19.

The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2.

Interleukin-13: A pivotal target against influenza-induced exacerbation of chronic lung diseases.

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.

Smoking and COVID-19: What we know so far.

The ongoing COVID-19 pandemic has placed a spotlight on infectious diseases and their associations with host factors and underlying conditions. New data on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus are entering the public domain at a rapid rate such that their distillation often lags behind. To minimise weak associations becoming perceived as established paradigms, it is imperative that methodologies and outputs from different studies are appropriately critiqued and compared. In this review, we examine recent data on a potential relationship between smoking and COVID-19. While the causal role of smoking has been firmly demonstrated in regard to lung cancer and chronic obstructive pulmonary disease, such associations have the benefit of decades' worth of multi-centre epidemiological and mechanistic data. From our analysis of the available studies to date, it appears that a relationship is emerging in regard to patients with a smoking history having a higher likelihood of developing more severe symptoms of COVID-19 disease than non-smokers. Data on whether COVID-19 has a greater incidence in smokers than non-smokers is thus far, contradictory and inconclusive. There is therefore a need for some caution to be exercised until further research has been conducted in a wider range of geographical settings with sufficient numbers of patients that have been carefully phenotyped in respect of smoking status and adequate statistical control for confounding factors.

The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders.

Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome-induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress- and inflammasome-related inflammatory disorders.

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

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 (Css min) 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 Css min and after a 5-day washout period to determine the endogenous glucosamine levels (GlcNend). The Actual Css min was calculated by using the following equation: Actual Css min = Observed Css min - GlcNend. 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 Css min levels (3-320 ng/mL) in participants. No significant association of Actual Css min 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.

A novel and sensitive HILIC-CAD method for glucosamine quantification in plasma and its application to a human pharmacokinetic study.

The clinical effect of glucosamine, the most widely used supplement in patients with osteoarthritis, on joint pain and function improvement, is reported to be inconsistent. Inter-patient variability in the pharmacokinetics of glucosamine, especially its oral absorption, could contribute to the inconsistent clinical outcomes. To test this hypothesis, a novel but simple Hydrophilic Interaction Liquid Chromatography coupled with Charged Aerosol Detector method was developed and validated. The sample was prepared by simple protein precipitation and analysed using an amino column and acetonitrile:100 mM ammonium formate with gradient elution. The developed method was linear (12.5-800 ng/mL, r2 = 0.999) and the relative standard deviations for intra- and inter-day accuracy, precision and repeatability were all less than 6%. The sensitivity of the method (lower limit of quantitation; 12.5 ng/mL) allowed the quantification of endogenous and exogenous glucosamine levels in 12 patients with osteoarthritis, taking 1500 mg glucosamine daily. The analysis showed 120-fold variation (81.7% variance) in exogenous glucosamine levels among the patients, indicating that substantial variability in the extent of absorption and/or rate of elimination could be a possible cause for the reported inconsistent clinical outcomes. The newly-developed method was sensitive and can be used to study the pharmacokinetics of glucosamine.