scholarly journals In vivo study of pharmacokinetic parameters of a new combination drug based on citicoline and memantine

2021 ◽  
Vol 7 (2) ◽  
pp. 23-30
Author(s):  
Boris B. Sysuev ◽  
Damir K. Salakhetdinov
Keyword(s):  
Blood Plasma ◽  
Maximum Concentration ◽  
Brain Diseases ◽  
New Combination ◽  
Pharmacokinetic Parameters ◽  
Combination Drug ◽  
Pharmaceutical Ingredients ◽  
Pharmaceutical Substances ◽  
In Blood Plasma

Introduction: Cognitive impairment (dementia) is one of the most common pathologies with increasing numbers of patients. Most often they are the symptoms of Alzheimer’s disease and vascular brain diseases, for which such drugs as memantine and citicoline are used. The development of a combination drug with these active pharmaceutical ingredients can significantly increase the effectiveness of therapy. Materials and methods: The pharmacokinetics of memantine and citicoline combination drug was evaluated in comparison with the marketed drugs (reference drugs) of these pharmaceutical substances approved for medical use by determining their content in blood plasma of experimental animals after a single oral administration. Results: Seventy-two hours after the administration of memantine drug, about 5% and 17% of the maximum concentration of memantine released from Akatinol Memantine and the developed combination drug were found in blood plasma, respectively. By the 120th hour after the beginning of the experiment, no memantine was detected in blood plasma of any animal. By the 24th hour after the beginning of the experiment, about 46% and 50% of the maximum concentration of citicoline released from the developed combination drug and the Ceraxon drug were found in blood plasma of the rabbits, respectively. Discussion: It was detected that the amounts of released memantine and citicoline from the developed combination drug exceeded the amounts of the appropriate pharmaceutical substances released from the reference drugs. The bioavailability of these substances from the developed combination drug was higher than from the marketed mono formulations used as reference drugs. Conclusion: Based on the obtained results of memantine and citicoline concentrations in bioassays, the main pharmacokinetic parameters of the studied preparations were calculated, the results of which showed the superiority of the developed combination drug over the reference drugs.

scholarly journals Analysis of Pharmacokinetic Parameters of Acetylsalicylic Acid for Prediction of Potential Nephrotoxic Effects

2021 ◽  
Vol 9 (4) ◽  
pp. 209-215
Author(s):  
L. M. Krasnykh ◽  
O. A. Goroshko ◽  
G. F. Vasilenko ◽  
G. I. Gorodetskaya ◽  
V. V. Smirnov ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Acetylsalicylic Acid ◽  
Blood Plasma ◽  
Maximum Concentration ◽  
Test Procedure ◽  
Elimination Rate ◽  
Statistical Processing ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
In Blood Plasma

Nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, can have a dose-dependent nephrotoxic effect. The study of the pharmacokinetics of acetylsalicylic acid products will contribute to timely detection and correction of side effects caused by this medicinal product.The aim of the study was to evaluate potential nephrotoxic effects following a single oral administration of 75 mg of acetylsalicylic acid, based on the analysis of the pharmacokinetic parameters.Materials and methods: the study involved 24 healthy volunteers who received 75 mg of acetylsalicylic acid (tablets) once orally. The measurement of the active metabolite of acetylsalicylic acid—salicylic acid—in blood plasma was performed by HPLC/MS using an Agilent 1200 liquid chromatography system coupled to an Agilent 6140 tandem mass spectrometer. Agilent Eclipse XDB-C18 column (4.6 mm×150 mm; 5.0 μm) was used for chromatographic separation. The test procedure used in the study was validated. The results obtained were used to calculate the pharmacokinetic parameters: Cmax (maximum concentration), Tmax (time to maximum concentration), T1/2 (half-life of the drug), AUC0-t (area under the pharmacokinetic curve from 0 to the last time point of the curve), AUC0-∞ (total area under the pharmacokinetic curve from 0 to ∞), MRT (mean residence time of the drug in the blood), Kel (elimination rate constant), Cl/F (total clearance), Vd/F (apparent volume of distribution). The Statistics (22.0.0.0) software was used for statistical processing of the results.Results: T1/2 of salicylic acid in blood plasma was determined to be 1.6 ± 0.5 h, Cmax was 4523.0 ± 725.0 ng/mL, and Tmax was 0.98 ± 0.4 h. AUC0–t was equal to 16183.0 ± 3823.0 ng×h/m, Vd/F was 12.0 ± 3.1 L/kg, and MRT was 2.9 ± 0.6 h.Conclusions: the analysis of the pharmacokinetic parameters demonstrated a high absorption rate, intensive distribution, and moderate elimination rate of salicylic acid (the main metabolite of acetylsalicylic acid), indicating a low risk of nephrotoxic effects associated with the studied dose of the drug.

scholarly journals Screening of lung cancer biomarker-proteins with a multiplex electrochemical sensor system based on aptamers

2018 ◽  
Vol 17 (3) ◽  
pp. 13-21
Author(s):  
Yu. E. Glazyrin ◽  
A. V. Shabalina ◽  
K. A. Ryginskaya ◽  
S. S. Zamay ◽  
V. A. Kolovski ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Blood Plasma ◽  
Simultaneous Detection ◽  
Selection Procedure ◽  
Cancer Tissue ◽  
Dna Aptamers ◽  
Affinity Enrichment ◽  
In Blood Plasma

The aimof this work is the development and demonstration of the method of simultaneous detection of several biomarkers of lung cancer in the blood plasma of patients using a multiplex electrochemical testing system based on DNA aptamers. DNA aptamers are a new class of synthetic affinity probes obtained by in vitro or in vivo selection procedure by the systematic evolution of ligands by exponential enrichment (SELEX).Materials and methods.A set of aptamers obtained previously by selection for postoperative lung cancer tissue was used to create a multiplex electrochemical biochip. Identification of aptamer target proteins was performed using a modified affinity enrichment method (AptaBID). Molecular targets for the used set of aptamers to lung cancer were defined as vimentin, defensin, a light chain of myosin, tubulin alpha 1-B, neutrophil elastase and A1 elongation factor 1.Measurements of the presence of these biomarker proteins in blood plasma were carried out using electrochemical detection. The difference between peak heights before and after plasma deposition on the electrodes modified by aptamers was considered as a response of the system to the presence of protein onco-markers in blood plasma. Blood plasma of healthy volunteers was used as control.Results. Research showed that in the blood plasma of all the patients with lung cancer the content of biomarker proteins that bind to aptamers on electrode surfaces was increased. The increased content of these proteins in the blood plasma of patients suggests the presence of invasiveness and metastasis of tumors and their chemo-resistance.

Method for Determining ε-Aminocaproic Acid (EACA) in Blood Plasma, Based on the Antifibrinolytic Properties of this Compound

1963 ◽  
Vol 10 (02) ◽  
pp. 309-316 ◽  
Author(s):  
Nina Wolosowicz ◽  
Stefan Niewiarowski ◽  
Kazimierz Czerepko
Keyword(s):  
Blood Plasma ◽  
Aminocaproic Acid ◽  
Clot Lysis ◽  
Boiling Water Bath ◽  
Trichloracetic Acid ◽  
Lysis Time ◽  
Ether Extraction ◽  
Clot Lysis Time ◽  
In Blood Plasma

SummaryA method was elaborated for determining e-aminocaproic acid (EACA) in blood plasma, based upon this compound’s antifibrinolytic activity.Oxalated plasma was deproteinized in a boiling water-bath using trichloracetic acid. The latter was removed from plasma filtrate by means of ether extraction and the effect of the deproteinized extract on clot fibrinolysis time under standard conditions was tested. There was found a linear correlation of the logarithm of clot lysis time with EACA concentration.The method appears to be fast and reliable, making possible serial determinations of the EACA level in blood plasma, the error being within the limits of 3 percent. It is suitable for the EACA level in plasma exceeding 2 mgVo.The method is most specific. Various amino acids appearing naturally (except cysteine) do not interfere with determinations.The EACA metabolism in vivo may be successfully studied using the above method.

Presence of 5-Hydroxytryptamine after Raunescine in Blood Plasma in vivo

Nature ◽  
1960 ◽  
Vol 185 (4706) ◽  
pp. 109-109 ◽  
Author(s):  
N. T. KÄRKI ◽  
M. K. PAASONEN
Keyword(s):  
Blood Plasma ◽  
In Blood Plasma

scholarly journals A Rapid and Sensitive UHPLC-MS/MS Method for Determination of 2, 3, 8-Trimethylellagic, a Potent Active Compound from Sanguisorba officinalis L., and Its Application in the Pharmacokinetic Study within Thrombocytopenia Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yuqing Wang ◽  
Jianming Wu ◽  
Yunxia Li ◽  
Jing Yang ◽  
Long Wang ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Maximum Concentration ◽  
High Performance ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Relative Standard ◽  
Plasma Concentration Time Curve

To investigate the pharmacokinetics of 2, 3, 8-trimethylellagic (TMEA) in rats in vivo and determine the possible effects of the pathological conditions and compatibility, a rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for quantitative determination was developed. TMEA and Artemetin (internal standard, IS) were separated on an Acquity Shim-pack GIST column with a total running time of 7 min using gradient elution at a flow rate of 0.3 mL/min. The intraday and interday relative standard deviations were <9.50%, and the relative error of accuracy was between −5.70% and 2.96%. The calibration curve of TMEA demonstrated good linearity with r2 = 0.9996, with the average recovery changing from 94.77% to 102.47% and the matrix effect from 93.16% to 100.15%. Compared with the normal group, the area under the plasma concentration-time curve from time 0 to the last time of quantifiable concentration (AUC(0 − t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0 − ∞)), and the maximum concentration (Cmax) of TMEA increased, whereas the time of maximum concentration (Tmax) and apparent clearance (CL/F) remarkably decreased in the TMEA group. With significantly reduced CL/F, AUC(0 − t), AUC(0 − ∞), and Cmax for TMEA were increased approximately one time after combining with 3, 7-Di-O-methylducheside A (DOMA). AUC(0 − t) and Cmax for TMEA in the 2, 3, 8-trimethylellagic-3, 8-dimethoxyellagic acid-2-oxyglucoside (TMEA-DMAG) group were significantly lower than that in the TMEA group with clearly prolonged Tmax and increased CL/F. These findings indicate that the changes in the pharmacokinetic parameters of TMEA may be caused by pathological and combination conditions.

scholarly journals How much LH do the Leydig cells see?

2002 ◽  
Vol 175 (2) ◽  
pp. 375-382 ◽  
Author(s):  
BP Setchell ◽  
P Pakarinen ◽  
I Huhtaniemi
Keyword(s):  
Endothelial Cells ◽  
Blood Plasma ◽  
Leydig Cells ◽  
Interstitial Fluid ◽  
Venous Blood ◽  
Extracellular Fluid ◽  
Significant Rise ◽  
Testicular Cells ◽  
In Blood Plasma

The purpose of this study was to assess the concentrations of LH that Leydig cells are exposed to upon in vivo stimulation of steroidogenesis. The concentrations of LH were measured in rats in testicular interstitial extracellular fluid, seminiferous tubular fluid and blood plasma from testicular veins from one testis before and from the other testis of the same rats after an intravenous injection of gonadotrophin-releasing hormone (GnRH) or saline, and compared with the concentrations in blood plasma from a peripheral vein. The concentrations of LH in interstitial fluid surrounding the Leydig cells before the injections were about 10% of the levels in blood plasma, and showed no significant rise at 15 min and a much smaller rise at later times in rats injected with GnRH than those seen in blood plasma from either of the two sources, which were similar. The concentrations of LH in tubular fluid were even lower and showed no change after GnRH. Testosterone concentrations in testicular cells, interstitial fluid and testicular venous blood plasma were significantly increased by 15 min after GnRH, when compared with saline-injected controls, with no change in the levels in tubular fluid. The rise in testosterone concentrations in testicular venous plasma after GnRH was smaller than those in the cells and interstitial fluid. In conclusion, the concentrations of LH reaching the testicular interstitial fluid were only about one-tenth of that measured in the circulation, presumably because the endothelial cells restrict access of the hormone to the interstitial fluid. This indicated that either the Leydig cells are extremely sensitive to LH stimulation or that testicular endothelial cells modulate the action of LH on the Leydig cells.

scholarly journals Individual features of the pharmacokinetics of fludarabin phosphate in the treatment of patients with chronic lymphocytic leukemia

2021 ◽  
pp. 67-77
Author(s):  
G. G. Rodionov ◽  
I. I. Shantyr ◽  
V. B. Vasilyuk ◽  
E. A. Kolobova ◽  
E. V. Svetkina ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Quantitative Determination ◽  
Blood Plasma ◽  
B Cell ◽  
Individual Variability ◽  
Lymphocytic Leukemia ◽  
Pharmacokinetic Parameters ◽  
Cell Chronic Lymphocytic Leukemia ◽  
In Blood Plasma

Fludarabine is a purine antimetabolite with a pronounced immunosuppressive effect. The inhibitory effect of fludarabine depends on its concentration in blood plasma. In addition, the phenotypic characteristics of patients affect the pharmacokinetic and pharmacodynamic profile of the drug, which necessitates a personalized approach to the dosage regimen. The chromatography-mass spectrometric method for the quantitative determination of 2-fluorine in blood plasma was developed for studying the individual parameters of pharmacokinetics of the international non-proprietary name (INN) fludarabine in patients with B-cell chronic lymphocytic leukemia during the standard course. Such method for the quantitative determination of 2-fluorine in blood plasma was developed and validated in accordance with international requirements. Significant individual variability of the main pharmacokinetic parameters in patients with B-cell chronic lymphocytic leukemia with a single oral administration of the drug with INN fludarabine at a dose of 40 mg/m2 was established, so the coefficient of variability Cmax was 42 %, Tmax — 92 %, AUC0-t — 45 %, Kel — 23 %, T1/2 — 26 %. It should be noted that there is a high interindividual variability of fludarabine, for example, 24 hours after taking the study drug, the maximum and minimum plasma concentrations of the fludarabine metabolite 2-fluoro-ara-A in different in patients with B-cell chronic lymphocytic leukemia differed 9 times. Individual variability of pharmacokinetic parameters characterizing absorption (Cmax/AUC0-t) and total clearance of the active metabolite of fludarabine is statistically significantly associated with a combination of gender and anthropometric factors.

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