The study of systemic exposition of 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide in blood on rats

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.11.529

Abstract

Introduction: The 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (ODASA) is new antiglaucoma drug. The compounds similar in structure are able to accumulate in red blood cells. Therefore, it is necessary to evaluate the pharmacokinetic parameters of ODASA and its metabolite in whole blood of laboratory animals. Aim: Calculation of pharmacokineticparameters of ODASA and its metabolites in rat whole blood after ocular instillation andintraperitoneal injection of the drug.

Materials and Methods: The 1% ocular suspension of ODASA was instilled into each eye in a volume of 20 µL to a group of 6 Wistar rats. The drug was also administrated by intraperitoneal injection at a dose of 1.6 mg/kg to another group of 6 Wistar rats. Sampling was carried out before administration and at 16 points for 288 hours after administration. HPLC-MS/MS was used for quantification of ODASA and its metabolites 4-[5-(hydroxymethyl)-1,3,4-oxadiazole-2-yl]-benzenesulfonamide (M1) and N-hydroxy-4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide (M2).

Results: The high concentration level of ODASA and M1 was observed: maximum blood concentration (Cmax) of ODASA after eye instillation was 10326±532 ng/mL, Cmax of M1 was 3722±505 ng/mL(M±SEM). The Cmax value of M2 was lower – 49.9±9.4 ng/mL (M±SEM). The half-life time of the studied compounds was more than 69 h. M1 has the greatest affinity for red blood cells. The value of the area under the “concentration-time” curve (AUC0-t) of M1 in bloodwas more than 150 times higher than AUC0-t of M1 in plasma.

Conclusion: The ODASA and its metabolites have long half-life time and high exposition in blood in comparison with that in plasma, which proves their accumulation in red blood cells.

Graphical Abstract

Keywords:

HPLC-MS/MS, whole blood, validation, pharmacokinetics, bioavailability, rats, carbonic anhydrase II inhibitor, N-hydroxysulfonamide

References

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Author Contribution

Alexander L. Khokhlov, Yaroslavl State Medical University

Doctor Habil. of Medical Sciences, Professor, Member of The Russian Academy of Sciences, Head of the Department of Pharmacology and Clinical Pharmacology, rector of Yaroslavl State Medical University; e-mail: al460935@yandex.ru; ORCID ID https://orcid.org/0000-0002-0032-0341. The author’s contribution: formulation and development of the aim and objectives; analysis and interpretation of the obtained data; critical review of the draft copy and provision of valuable comments.

Ilya I. Yaichkov, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Candidate of Pharmaceutical Sciences, research fellow of the Department of Analytical Development and Quality Control of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky; research fellow of the Institute of Pharmacy of Yaroslavl State Medical University; e-mail: i.yaichkov@yspu.org; ORCID ID https://orcid.org/0000-0002-0066-7388. The author’s contribution: concept development; development of design of pharmacokinetic study; development of bioanalytical methods; analysis of samples; analysis and interpretation of the obtained data; writing the bioanalytical part and editing the manuscript.

Anton A. Shetnev, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Candidate of Chemical Sciences, Head of the Department of Pharmaceutical Development of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical Universitynamed after K.D. Ushinsky; e-mail: a.shetnev@list.ru; ORCID ID https://orcid.org/0000-0002-4389-461X. The author’s contribution: synthesis of substances of the drug and its metabolites.

Mikhail K. Korsakov, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Doctor Habil. of Chemical Sciences, Professor of the Department of Chemistry, Theory and Methods of Teaching Chemistry, Head of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky; e-mail: m.korsakov@yspu.org; ORCID ID https://orcid.org/0000-0003-0913-2571. The author’s contribution: formulation and development of the aim and objectives; analysis and interpretation of the obtained data; critical review of the draft copy and provision of valuable comments.

Nikita N. Volkhin , Yaroslavl State Medical University

Assistant of the Department of Pharmacology and Clinical Pharmacology of Yaroslavl State Medical University; junior research fellow of the Department of Pharmacological Studies of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical Universitynamed after K.D. Ushinsky; e-mail: nnvolkhin@ysmu.ru; ORCID ID https://orcid.org/0000-0002-4275-9037. The author’s contribution: working with laboratory animals; blood and plasma sample collection.

Sergey S. Petukhov, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Engineer of the Department of Pharmacological Studies of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky; junior research fellow of the Institute of Pharmacy of Yaroslavl State Medical University; e-mail:sspp465@mail.ru; ORCID ID https://orcid.org/0009-0007-8435-7689. The author’s contribution: working with laboratory animals; blood and plasma sample collection.

Alena N. Tyushina, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Engineer of the Department of Pharmacological Studies of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky; junior research fellow of the Institute of Pharmacy of Yaroslavl State Medical University; e-mail:denezhkina89@mail.ru; ORCID ID https://orcid.org/0009-0007-8084-5239. The author’s contribution: working with laboratory animals; blood and plasma sample collection.

Olga E. Lasaryanz, Yaroslavl State Pedagogical University named after K.D. Ushinsky

Engineer of the Department of Pharmacological Studies of M.V. Dorogov Pharmaceutical Technology Transfer Center of Yaroslavl State Pedagogical University named after K.D. Ushinsky; specialist of the Institute of Pharmacy of Yaroslavl State Medical University; e-mail: lazaryants98@mail.ru; ORCID ID https://orcid.org/0009-0002-1249-3669. The author’s contribution: working with laboratory animals; blood and plasma sample collection.

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Published

29-06-2025

How to Cite

Khokhlov AL, Yaichkov II, Shetnev AA, Korsakov MK, Volkhin NN, Petukhov SS, Tyushina AN, Lasaryanz OE (2025) The study of systemic exposition of 4-(5-methyl-1,3,4-oxadiazole-2-yl)-benzenesulfonamide in blood on rats. Research Results in Pharmacology 11(2): 100–111. https://doi.org/10.18413/rrpharmacology.11.529

Issue

Vol. 11 No. 2 (2025)

Section

Experimental Pharmacology

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Copyright (c) 2025 Khokhlov AL, Yaichkov II, Shetnev AA, Korsakov MK, Volkhin NN, Petukhov SS, Tyushina AN, Lasaryanz OE

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