Pharmacokinetic parameters of a zinc complex with N‑allylimidazole

Victoria S.  Babasieva; Vladislav N. Turenko; Andrey R. Grabeklis; Dmitry M. Lyapunovsky; Anatoly  V. Skalny; Vladimir S. Tyurin; David E. Bagaev; Victoria G. Krasnyanskaya; Galina F. Vasilenko; Obinna Ikebunwa; Valery V. Smirnov; Svetlana A. Lebedeva

doi:10.18413/rrpharmacology.12.1240

Authors

Victoria S. Babasieva Sechenov First Moscow State Medical University (Sechenov University), Moscow https://orcid.org/0000-0003-2846-4133
Vladislav N. Turenko Sechenov First Moscow State Medical University (Sechenov University); Allergy and Immunology Research Centre FMBA of Russia https://orcid.org/0000-0003-1817-0844
Andrey R. Grabeklis People's Friendship University of Russia named after Patrice Lumumba (RUDN University) https://orcid.org/0000-0003-4017-4139
Dmitry M. Lyapunovsky People's Friendship University of Russia named after Patrice Lumumba (RUDN University) https://orcid.org/0009-0003-4863-1792
Anatoly V. Skalny People's Friendship University of Russia named after Patrice Lumumba (RUDN University) https://orcid.org/0000-0001-7838-1366
Vladimir S. Tyurin Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Science https://orcid.org/0000-0002-8663-2935
David E. Bagaev Sechenov First Moscow State Medical University (Sechenov University); Allergy and Immunology Research Centre FMBA of Russia https://orcid.org/0009-0008-5495-7939
Victoria G. Krasnyanskaya Allergy and Immunology Research Centre FMBA of Russia https://orcid.org/0000-0001-7604-8172
Galina F. Vasilenko Allergy and Immunology Research Centre FMBA of Russia https://orcid.org/0000-0001-7940-1664
Obinna Ikebunwa Sechenov First Moscow State Medical University (Sechenov University); Michigan State University https://orcid.org/0009-0006-5619-5531
Valery V. Smirnov Sechenov First Moscow State Medical University (Sechenov University); Allergy and Immunology Research Centre FMBA of Russia https://orcid.org/0000-0002-8232-6682
Svetlana A. Lebedeva Sechenov First Moscow State Medical University (Sechenov University); People's Friendship University of Russia named after Patrice Lumumba (RUDN University); Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology https://orcid.org/0000-0001-8769-1040

DOI:

https://doi.org/10.18413/rrpharmacology.12.1240

Abstract

Introduction: Zinc is an essential trace element with well-known physiological functions. Although various zinc salts are available, novel zinc complexes with organic ligands remain of pharmacological interest. Pharmacokinetic studies are essential to clarify the contribution of the zinc ion and organic ligand to their biological activity.

Materials and Methods: The pharmacokinetics of bis(N-allylimidazole) zinc diacetate (ALL) components were studied in 66 BALB/c mice. The compound was administered once intraperitoneally at 25 mg/kg. Blood, brain, liver, pancreas, kidneys, and spleen were collected at 0, 0.083, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 24 h, with 6 animals per time point. N-allylimidazole was quantified using a validated HPLC-MS/MS method, while zinc was determined by atomic absorption spectrometry.

Results and Discussion: ALL likely dissociates into N-allylimidazole and zinc under physiological conditions, resulting in distinct pharmacokinetic profiles. N-allylimidazole was detected in all tissues, including the brain. The Tmax for most tissues was 0.25 h, indicating rapid systemic distribution. The highest concentration was observed in the kidneys (Cmax 7907.58 µg/g), suggesting their involvement in ligand excretion. In the liver, N-allylimidazoleshowed prolonged retention, with a T1/2 of 14.5 h and AUC(0–24) of 11168.41 µg·h/mL. After correction for endogenous zinc, the highest zinc concentrations were detected in the liver (60.21 µg/g), pancreas (57.52 µg/g), and spleen (54.80 µg/g).

Conclusion: ALL administration resulted in rapid systemic distribution of both components. N-allylimidazole penetrated highly perfused tissues, including the brain and kidneys, whereas zincaccumulated in the liver, pancreas, and spleen. Distinct tissue distribution and elimination profiles, together with equilibrium calculations, support complete in vivo dissociation of the complex.

Graphical Abstract

Keywords:

zinc, N-allylimidazole, pharmacokinetics, HPLC-ESI-MS/MS, atomic absorption spectrometry

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Author Contribution

Victoria S. Babasieva, Sechenov First Moscow State Medical University (Sechenov University), Moscow

PhD student, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; e-mail: victoriababasieva@mail.ru; ORCID ID: https://orcid.org/0000-0003-2846-4133. Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft.

Vladislav N. Turenko, Sechenov First Moscow State Medical University (Sechenov University); Allergy and Immunology Research Centre FMBA of Russia

Junior researcher, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia; e-mail: turenko.n@gmail.com; ORCID ID: https://orcid.org/0000-0003-1817-0844. Conceptualization, Investigation, Methodology, Validation, Writing – Original Draft.

Andrey R. Grabeklis, People's Friendship University of Russia named after Patrice Lumumba (RUDN University)

Senior researcher, People's Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow, Russia; e-mail: grabeklis-ar@rudn.ru; ORCID ID: https://orcid.org/0000-0003-4017-4139.

Dmitry M. Lyapunovsky, People's Friendship University of Russia named after Patrice Lumumba (RUDN University)

PhD student, People's Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow, Russia; e-mail: lyapunovskiy-dm@rudn.ru; ORCID ID: https://orcid.org/0009-0003-4863-1792. Investigation, Methodology.

Anatoly V. Skalny, People's Friendship University of Russia named after Patrice Lumumba (RUDN University)

MD, PhD, Head of Department at Peoples' Friendship University of Russia, People's Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow, Russia; e-mail: skalnyy-av@rudn.ru; ORCID ID: https://orcid.org/0000-0001-7838-1366. Supervision.

Vladimir S. Tyurin, Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Science

Senior researcher, Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, Russia; e-mail: tv@org.chem.msu.ru; ORCID ID: https://orcid.org/0000-0002-8663-2935. Formal Analysis, Writing – Review & Editing.

David E. Bagaev, Sechenov First Moscow State Medical University (Sechenov University); Allergy and Immunology Research Centre FMBA of Russia

Junior researcher, Institute of Pharmacy,cSechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia; e-mail: bagaev3411302@mail.ru; ORCID ID: https://orcid.org/0009-0008-5495-7939.

Victoria G. Krasnyanskaya, Allergy and Immunology Research Centre FMBA of Russia

Laboratory assistant, National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russian Federation; e-mail: lec@nrcii.ru; ORCID ID: https://orcid.org/0000-0001-7604-8172.

Galina F. Vasilenko, Allergy and Immunology Research Centre FMBA of Russia

Researcher, National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia; e-mail: lec@nrcii.ru; ORCID ID: https://orcid.org/0000-0001-7940-1664.

Obinna Ikebunwa, Sechenov First Moscow State Medical University (Sechenov University); Michigan State University

PhD student, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; Department of Pharmacology and Toxicology, Michigan State University, Michigan, USA; e-mail: ikebunwaobinna@gmail.com; ORCID ID: https://orcid.org/0009-0006-5619-5531. Investigation, Data Curation.

Valery V. Smirnov, Sechenov First Moscow State Medical University (Sechenov University); Allergy and Immunology Research Centre FMBA of Russia

Dr. Sci, Professor, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia; e-mail: vall@mail.mipt.ru; ORCID ID: https://orcid.org/0000-0002-8232-6682. Supervision.

Svetlana A. Lebedeva, Sechenov First Moscow State Medical University (Sechenov University); People's Friendship University of Russia named after Patrice Lumumba (RUDN University); Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology

Dr. Sci, Professor, Institute of Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; People's Friendship University of Russia named after Patrice Lumumba (RUDN University), Moscow, Russia; Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, Sirius, Russia; e-mail: Lebedeva502@yandex.ru; ORCID ID: https://orcid.org/0000-0001-8769-1040. Supervision, Visualization, Writing – Review & Editing.