Naproxen glycine conjugate-synthesis, pharmaceutical preformulation and pharmacodynamic evaluation

Drug Delivery ◽  
2012 ◽  
Vol 19 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Ashutosh Mishra ◽  
Shalini Agrawal ◽  
Kamla Pathak
Keyword(s):  
Glycine Conjugate

Hyperprolinemia type II: identification of the glycine conjugate of pyrrole-2-carboxylic acid in urine

1977 ◽  
Vol 10 ◽  
pp. 20-23 ◽  
Author(s):  
Derek A. Applegarth ◽  
Stephen I Goodman ◽  
Donald G. Irvine ◽  
Egil Jellum
Keyword(s):  
Carboxylic Acid ◽  
Type Ii ◽  
Glycine Conjugate ◽  
Hyperprolinemia Type Ii

scholarly journals Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes

2018 ◽  
Author(s):  
Klev Diamanti ◽  
Marco Cavalli ◽  
Gang Pan ◽  
Maria J Pereira ◽  
Chanchal Kumar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Deoxycholic Acid ◽  
Organ Donors ◽  
Additional Increase ◽  
Tissue Samples ◽  
Molecular Defects ◽  
Glycine Conjugate ◽  
Metabolic Screening ◽  
Unique Dataset

ABSTRACTType-2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from a cohort of 43 multi-organ donors. The intra-individual analysis was assessed across five key-metabolic tissues (serum, adipose tissue, liver, pancreatic islets and muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. Carnitines were significantly higher in liver, while lysophosphatidylcholines significantly lower in muscle and serum. An investigation of the progression to overt T2D showed that deoxycholic acid glycine conjugate was significantly higher in liver of pre-diabetes samples while additional increase in T2D was insignificant. A subset of lysophosphatidylcholines were significantly lower in the muscle of pre-diabetes subjects. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

Differential effects of calcium ions and calcium phosphate on cytotoxicity of bile acids

1991 ◽  
Vol 260 (1) ◽  
pp. G142-G147 ◽  
Author(s):  
R. Van der Meer ◽  
D. S. Termont ◽  
H. T. De Vries
Keyword(s):  
Bile Acid ◽  
Calcium Phosphate ◽  
Bile Acids ◽  
Colonic Mucosa ◽  
Molecular Mechanisms ◽  
Epithelial Proliferation ◽  
Cytotoxic Potential ◽  
Glycine Conjugate ◽  
Taurine Conjugate ◽  
Secondary Bile Acids

Unconjugated secondary bile acids can promote colon cancer by damaging colonic mucosa and consequently increasing epithelial proliferation. It has been proposed that dietary calcium inactivates intestinal bile acids either by a Ca2(+)-dependent precipitation or by binding to insoluble calcium phosphate (CaPi). We studied the molecular mechanisms of these opposing hypotheses by using hemolysis of erythrocytes as a model parameter for cytotoxicity. Washed human erythrocytes were incubated for 15 min with buffered media (pH 7.4) containing increasing amounts of different bile acids. Deconjugation and 7 alpha-dehydroxylation of mixtures of glycine- or taurine-conjugated cholate and chenodeoxycholate drastically increased their cytotoxicity. Parallel measurements, using a fluorescent micellar probe, indicated that micellar aggregation is a prerequisite for this bile acid-induced lysis. Ca2+ concentrations up to 15 mM did not precipitate bile acids but stimulated cytotoxicity of both deoxycholate (DC) and its glycine conjugate (GDC). Cytotoxicity of the taurine conjugate (TDC) was stimulated to a much lesser extent. Increasing amounts of CaPi precipitated micellar DC and GDC, but not TDC, and consequently inhibited only cytotoxicity of the former two. These findings indicate that 1) hydrophobicity and micellar aggregation are important determinants of bile acid-induced cytotoxicity that explain the high cytotoxic potential of secondary bile acids in colon, and 2) cytotoxicity of bile acids is stimulated by free Ca2+ and inhibited by CaPi. This inhibition is due to binding of carboxylic (including secondary) bile acids to CaPi.

Metabolism of Aspirin after Therapeutic and Toxic Doses

1990 ◽  
Vol 9 (3) ◽  
pp. 131-136 ◽  
Author(s):  
D.K. Patel ◽  
A. Hesse ◽  
A. Ogunbona ◽  
L.J. Notarianni ◽  
P.N. Bennett
Keyword(s):  
Salicylic Acid ◽  
Therapeutic Dose ◽  
Urinary Metabolites ◽  
Urinary Recovery ◽  
Main Metabolite ◽  
Gentisic Acid ◽  
Salicyluric Acid ◽  
Glycine Conjugate ◽  
Kinetics Of

1 The urinary recovery of metabolites of aspirin (ASA) was studied in 45 volunteers who took a therapeutic dose (600 mg) of ASA by mouth and in 37 patients who took ASA in overdose. 2 The main metabolite recovered from the volunteers was the glycine conjugate, salicyluric acid (SUA), which accounted for 75.01 ± 1.19% of total urinary metabolites, whereas salicylic acid (SA) accounted for 8.82 ± 0.56%. Recovery of SUA was negatively correlated with that of SA (r = -0.8625, P < 0.001). 3 In 24 patients with admission plasma salicylate concentrations of 240-360 mg 1-1, SUA accounted for 46.66 ± 3.22% and SA for 31.88 ± 4.02%. 4 In 13 patients with admission plasma salicylate concentrations of 715-870 mg 1-1, SUA accounted for 21.57 ± 3.65% and SA for 64.72 ± 4.82%. 5 Reduced excretion of salicylate as SUA was also accompanied by increased elimination as gentisic acid and salicylic acid phenolic glucuronide indicating that the unsaturated processes that lead to the formation of these metabolites contribute significantly (22-23%) to the inactivation of large doses of salicylate. 6 While the Michalis-Menten kinetics of ASA have been well demonstrated at lower doses, our findings illustrate the progressive saturation of SUA formation under conditions of increasing ASA load to toxic amounts and raise issues about the in-vivo glycine pool when ASA is taken in overdose.

scholarly journals Hydroxyproline Metabolism in Type II Hyperprolinaemia

1979 ◽  
Vol 16 (1-6) ◽  
pp. 177-181 ◽  
Author(s):  
S. Similä
Keyword(s):  
Carboxylic Acid ◽  
Plasma Level ◽  
Urinary Excretion ◽  
Healthy Controls ◽  
Type Ii ◽  
Elevated Plasma ◽  
Hydroxyproline Concentration ◽  
Glycine Conjugate ◽  
Hydroxyproline Metabolism ◽  
Very High

Hydroxyproline metabolism was studied in two patients with type II hyperprolinaemia (HP II) using oral loadings of hydroxyproline or hydroxyproline-ornithine. Δ1-pyrroline-3-hydroxy-5-carboxylic acid (3 OH-PC) and Δ1-pyrroline-5-carboxylic acid (PC) were identified in the urine. The urinary excretion of both 3-OH-PC and PC increased in HP II patients but not in healthy controls during oral loading of hydroxyproline and hydroxyproline-ornithine. The plasma level of proline in patients with HP II is very high but the hydroxyproline concentration is normal or only slightly increased. Therefore one can assume that hydroxyproline is converted to pyrrole-2-carboxylic acid, which is excreted in urine as a glycine conjugate. In this study it was demonstrated that the highly elevated plasma level of proline in one of the patients with HP II decreased greatly after hydroxyproline-ornithine load; this change was followed by a 40-fold rise in urinary excretion of proline.

scholarly journals Determination of obeticholic acid and its glycine conjugate in human plasma using liquid chromatography-tandem mass spectrometry

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2681-2687
Author(s):  
Muralikrishna Ramisetti ◽  
Lakshmana Rao Atmakuri ◽  
Rama Shekara Reddy Dachuru
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Human Plasma ◽  
Tandem Mass ◽  
Obeticholic Acid ◽  
Acceptance Criteria ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Glycine Conjugate

A sensitive and selective liquid chromatography/tandem mass spectrometry method was recommended by the authors for the determination orally bioavailable farnesoid X receptor agonist obeticholic acid along with its glycine conjugate glycoobeticholic acid human plasma. Obeticholic acid_d5 and glycoobeticholic acid_d5 were used as internal standards, respectively. After extraction with a mixture of tert-butyl methyl ether and dichloromethane, samples were separated on a phenyl column with a mobile phase of 2mM ammonium acetate with 0.01% formic acid and methanol (15:85, v/v). Analysis was performed on an AB Sciex 4500 triple quadrupole mass spectrometer and data acquisition was performed by multiple reaction monitoring (MRM) in the negative ionization mode. Obeticholic acid and its conjugate were quantified in the linearity range of 0.50-100.00 ng/mL and the correction coefficients were≥0.99 during the validation. Precision and accuracy in different days (inter-day) and single day (intra-day) were meeting the acceptance criteria specified in the recent US FDA bioanalytical method validation guidelines. A variety of stability experiments in neat samples and plasma samples were conducted and the results are meeting the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze a greater number of samples in a short time, thus increasing productivity. This method could be useful to quantitate obeticholic acid and glycoobeticholic acid in real clinical samples.

scholarly journals Excretion of benzoic acid derivatives in urine of sheep given intraruminal infusions of 3-phenylpropionic and cyclohexanecarboxylic acids

1997 ◽  
Vol 77 (4) ◽  
pp. 577-592 ◽  
Author(s):  
J. H. Pagella ◽  
X. B. Chen ◽  
N. A. Macleod ◽  
E. R. Ørskov ◽  
P. J. S. Dewey
Keyword(s):  
Benzoic Acid ◽  
Urinary Excretion ◽  
Hippuric Acid ◽  
Quantitative Relationship ◽  
The Other ◽  
Urinary Recovery ◽  
Faecal Excretion ◽  
Benzoic Acid Derivatives ◽  
Significant Linear Correlation ◽  
Glycine Conjugate

The quantitative relationship between the urinary excretion of benzoic acid (BA)and the uptake of 3-phenylpropionic (PPA) and cyclohexanecarboxylic (CHCA) acids was assessed.PPA and CHCA are produced in the rumen by microbial fermentation of lignocellulosic feeds and metabolized, after absorption, to BA which is excreted in the urine mainly as its glycine conjugate hippuric acid (HA). Four sheep nourished by intragastric infusions of all nutrients weregiven continuous ruminal infusions of PPA (8,16 or 24 mmol/d) either alone or with CHCA (8 or 16 mmol/d) in a factorial experiment. The treatments were allocated to ten consecutive 6 d periods, with a control being repeated at periods 1, 5 and 10. PPA and CHCA ruminal absorption rates, estimated using the liquid-phase marker Cr-EDTA, were 0·78 (SD 0·29)/h and 0·88 (SD 0·28)/h respectively. For the control, HA excretion was only 0·22 (SD 0·33) mmol/d and free BA was absent. For the other treatments, both HA and free BA were present and HA accounted for 0·85 (SD 0·05) of total BA. The urinary excretion of total BA showed a significant linear correlation (r = 0·997, P<0·001) with the amounts of PPA and CHCA infused. The urinary recovery of infused PPA and CHCA as total BA was 0·79 (SE 0·01). Faecal excretion of BA and its precursors was negligible. Results of this study show that urinary total BA is a potential estimator of the absorption of PPA + CHCA produced in the rumen

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