Determination of the immunostimulatory drug—glucosoaminyl‐muramyl‐dipeptide—in human plasma using HPLC–MS/MS and its application to a pharmacokinetic study

Article

Author: Kuznetsov, Roman M. ; Moskaleva, Natalia E. ; Markin, Pavel A. ; Appolonova, Svetlana A. ; Andronova, Tatiana M.

AbstractGMDP (glucosoaminyl‐muramyl‐dipeptide), a synthetic analog of the peptidoglycan fragment of the bacterial cell wall, is an active component of the immunomodulatory drug Licopid. But the pharmacokinetic parameters of GMDP in humans after oral administration have not been investigated yet. The present study aimed at developing and validating a sensitive LC–MS/MS method for the analysis of GMDP in human plasma. The sample was prepared by solid‐phase extraction using Strata‐X 33 μm polymeric reversed‐phase 60 mg/3 mL cartridges Phenomenex (Torrance, CA, USA). The analytes were separated using an Acquity UPLC BEN C18 column, 1.7 μm 2.1 × 50 mm Waters (Milford, USA). GMDP and internal standard growth hormone releasing peptide‐2 (pralmorelin) were ionized in positive electrospray ionization mode and detected in multiple reaction monitoring mode. The developed method was validated within a linear range of 50–3000 pg/mL for GMDP. Accuracy for all analytes, given as the deviation between the nominal and measured concentration and assay variability , ranged from 1.61 to 3.02% and from 0.89 to 1.79%, respectively, for both within‐ and between‐run variabilities. The developed and validated HPLC–MS/MS method was successfully used to obtain the plasma pharmacokinetic profiles of GMDP distribution in human plasma.

01 Jan 2019·Vestnik otorinolaringologii

Glucosaminylmuramyl dipeptide in treatment of respiratory tract diseases

Review

Author: Burkin, A V ; Nikiforova, G N ; Svistushkin, V M ; Dukhanin, A S

INTRODUCTIONImmunomodulators are used as part of a comprehensive therapy of respiratory tract diseases. The systematization of the accumulated data on the use of glucosaminylmuramyldipeptide (GMDP) has great scientific and practical interest.PURPOSETo study the data on the effectiveness and safety of GMDP in the treatment of infectious diseases of the respiratory tract.MATERIAL AND METHODSLiterature search was carried out in Scientific Electronic Library (elibrary.ru), Google Scholar, ScienceDirect, Cochrane library, Pubmed/MEDLINE and search engines. The level of evidence reliability and methodological quality of researches were assessed.RESULTS17 full-text publications were selected based on the results of 13 prospective clinical trials with acceptable methodological quality (including one blind placebo-controlled trial). The effectiveness of GMDP in acute respiratory viral infections, influenza, recurrent respiratory tract infections, rhinosinusitis and chronic tonsillitis was demonstrated.DISCUSSIONAn important advantage is that a significant part of the studies was performed with the participation of the child population. Since the use of GMDP in multiple therapy significantly reduces antibiotic consumption (often unjustified). It seems reasonable to estimate the pharmacoeconomic costs of managing adult patients with respiratory tract diseases. Further research can improve understanding of the role of GMDP in the treatment of various medical conditions.CONCLUSIONThe use of GMDP in the treatment of respiratory tract diseases makes it possible to faster achieve a clinical effect, reduce the number of relapses, lengthen the relapse-free period, as well as to potentiate the effect of antibacterial therapy (if necessary), reducing the need for antibiotics.

01 Sep 2018·Doklady Biochemistry and BiophysicsQ4 · BIOLOGY

Polyprenyl Phosphates Induce a High Humoral and Cellular Response to Immunization with Recombinant Proteins of the Replicative Complex of the Hepatitis C Virus

Q4 · BIOLOGY

Article

Author: Ivanov, A V ; Ivanova, A M ; Onishchuk, A A ; Lesnova, E I ; Gerasimova, E V ; Sanin, A V ; Kushch, A A ; Masalova, O V ; Pronin, A V ; Narovlyansky, A N

The search for new adjuvants remains the critical task for the creation of hepatitis C vaccines due to the weak immunogenicity of biotechnological products. When immunizing mice with the recombinant proteins NS3 and NS5B of the hepatitis C virus (HCV), the adjuvant activity of three immunomodulators was compared. Phosprenyl® on the basis of polyprenyl phosphate (PPP), chemically synthesized analogue of the bacterial cell wall glucosaminyl muramyl dipeptide (GMDP), and IFN-α recombinant protein were tested. GMDP increased the activity of IgG1 antibodies 4-6 times but did not stimulate the production of IFN-γ; IFN-α has not shown any adjuvant properties. The introduction of recombinant HCV proteins together with PPP in low doses increased the activity of IgG2a isotype antibodies 4-7 times and increased IFN-γ secretion 3 times. Thus, it was first shown that PPP polarizes the immune response to Th1-type and is a promising adjuvant for the development of a vaccine against hepatitis C.

100 Deals associated with Glycopin

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KEGG	Wiki	ATC	Drug Bank
-	-	L03	-

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Approved

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Indication	Country/Location	Organization	Date
Tuberculosis	RU	-	17 Nov 1998
Respiratory Diseases	RU	-	30 Jan 1998
Herpesviridae Infections	RU	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Psoriasis	RU	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Pulmonary Tuberculosis	RU	Teva Pharmaceutical Industries Ltd.	01 Sep 1996
Surgical Wound Infection	RU	Teva Pharmaceutical Industries Ltd.	01 Sep 1996

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Rhinitis	Preclinical	RU	Peoples' Friendship University of Russia	01 Feb 2019
Neutropenia	Preclinical	RU	-	-
Neutropenia	Preclinical	AU	-	-
Psoriasis	Preclinical	GB	-	-
Pyoderma	Preclinical	RU	-	-

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