Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits

Resume. Relevance. Ethylthiadiazolamide of acetylaminohexanoic acid is a new non-steroidal anti-inflammatory agent from derivative of 1, 3, 4-thiadiazole and acexamic acid. Purpose. Evaluation of the bioavailability of ethylthiadiazolamide of acetylaminohexanoic acid with single intragastric adminis...

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Main Authors: A. S. Malygin, N. S. Popov, M. A. Demidova, S. B. Marasanov
Format: Article
Language:Russian
Published: LLC “Publisher OKI” 2018-02-01
Series:Фармакокинетика и Фармакодинамика
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Online Access:https://www.pharmacokinetica.ru/jour/article/view/53
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author A. S. Malygin
N. S. Popov
M. A. Demidova
S. B. Marasanov
author_facet A. S. Malygin
N. S. Popov
M. A. Demidova
S. B. Marasanov
author_sort A. S. Malygin
collection DOAJ
description Resume. Relevance. Ethylthiadiazolamide of acetylaminohexanoic acid is a new non-steroidal anti-inflammatory agent from derivative of 1, 3, 4-thiadiazole and acexamic acid. Purpose. Evaluation of the bioavailability of ethylthiadiazolamide of acetylaminohexanoic acid with single intragastric administration to rabbits. Materials and Methods. Pharmacokinetic studies were performed using 6 rabbits of the Chinchilla breed. The study was conducted using an open, randomized, cross-sectional scheme. Ethylthiadiazolamide of acetylaminohexanoic acid was administered intravenously at a dose of 1 mg/kg in a 0.33 % solution of dimexide or intragastrically at a dose of 1 mg/kg in 20 ml of 2 % starch mucus. Determination of analyte in blood plasma was carried out by HPLC-MS/MS method. Sample preparation was carried out by the method of blood plasma protein precipitation by acetonitrile. Chromatography was performed with an analytical column Agilent InfinityLab Poroshell 120 EC-C18 2.7 |±m 4.6 x100 mm. As a mobile phase, a mixture of acetonitrile and deionized water at the ratio 30:70 with adding 0.1 % formic acid in the isocratic mode. The identification was carried out by mass spectrometry according to MRM m/z 285.2 → m/z 130.2. Results and Discussion. The maximum content of ethylthiadiazolamide of acetylaminohexanoic acid in blood plasma was 806.8 ± 65.6 ng/ml at 1.345 ± 0.081 h after intragastric administration. The area under the pharmacokinetic curve AUC0→36 was 5 088.1 ± 442.1 ngхh/ml, and the ratio AUC36→∞/AUC0→36 - 2,96 ± 1,59 %. Bioavailability of ethylthiadiazolamide of acetylaminohexanoic acid with intragastric administration to rabbits at a dose of 1 mg/kg as an aqueous suspension averaged 37 %. Conclusion. It is necessary to improve biopharmaceutical properties of ethylthiadiazolamide of acetylaminohexanoic acid to increase bioavailability.
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spelling doaj-art-545b5015f6eb4c28a9ad3c7ef5c759dd2025-08-20T03:20:16ZrusLLC “Publisher OKI”Фармакокинетика и Фармакодинамика2587-78362686-88302018-02-0101566310.24411/2587-7836-2018-10007.52Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbitsA. S. Malygin0N. S. Popov1M. A. Demidova2S. B. Marasanov3FSBEI HE Tver SMU MOH RussiaFSBEI HE Tver SMU MOH RussiaFSBEI HE Tver SMU MOH RussiaFSBEI HE Tver SMU MOH RussiaResume. Relevance. Ethylthiadiazolamide of acetylaminohexanoic acid is a new non-steroidal anti-inflammatory agent from derivative of 1, 3, 4-thiadiazole and acexamic acid. Purpose. Evaluation of the bioavailability of ethylthiadiazolamide of acetylaminohexanoic acid with single intragastric administration to rabbits. Materials and Methods. Pharmacokinetic studies were performed using 6 rabbits of the Chinchilla breed. The study was conducted using an open, randomized, cross-sectional scheme. Ethylthiadiazolamide of acetylaminohexanoic acid was administered intravenously at a dose of 1 mg/kg in a 0.33 % solution of dimexide or intragastrically at a dose of 1 mg/kg in 20 ml of 2 % starch mucus. Determination of analyte in blood plasma was carried out by HPLC-MS/MS method. Sample preparation was carried out by the method of blood plasma protein precipitation by acetonitrile. Chromatography was performed with an analytical column Agilent InfinityLab Poroshell 120 EC-C18 2.7 |±m 4.6 x100 mm. As a mobile phase, a mixture of acetonitrile and deionized water at the ratio 30:70 with adding 0.1 % formic acid in the isocratic mode. The identification was carried out by mass spectrometry according to MRM m/z 285.2 → m/z 130.2. Results and Discussion. The maximum content of ethylthiadiazolamide of acetylaminohexanoic acid in blood plasma was 806.8 ± 65.6 ng/ml at 1.345 ± 0.081 h after intragastric administration. The area under the pharmacokinetic curve AUC0→36 was 5 088.1 ± 442.1 ngхh/ml, and the ratio AUC36→∞/AUC0→36 - 2,96 ± 1,59 %. Bioavailability of ethylthiadiazolamide of acetylaminohexanoic acid with intragastric administration to rabbits at a dose of 1 mg/kg as an aqueous suspension averaged 37 %. Conclusion. It is necessary to improve biopharmaceutical properties of ethylthiadiazolamide of acetylaminohexanoic acid to increase bioavailability.https://www.pharmacokinetica.ru/jour/article/view/53нестероидные противовоспалительные средстваэтилтиадиазолиламид ацетиламиногексановой кислотыбиодоступностьвэжх-мс/мсnonsteroidal anti-inflammatory agentsethylthiadiazolamide of acetylaminohexanoic acidbioavailabilityhplc-ms/ms
spellingShingle A. S. Malygin
N. S. Popov
M. A. Demidova
S. B. Marasanov
Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
Фармакокинетика и Фармакодинамика
нестероидные противовоспалительные средства
этилтиадиазолиламид ацетиламиногексановой кислоты
биодоступность
вэжх-мс/мс
nonsteroidal anti-inflammatory agents
ethylthiadiazolamide of acetylaminohexanoic acid
bioavailability
hplc-ms/ms
title Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
title_full Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
title_fullStr Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
title_full_unstemmed Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
title_short Assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
title_sort assessment of bioavailability of ethylthiadiazolylamide of acetylaminohexanoic acid by intragastric administration in rabbits
topic нестероидные противовоспалительные средства
этилтиадиазолиламид ацетиламиногексановой кислоты
биодоступность
вэжх-мс/мс
nonsteroidal anti-inflammatory agents
ethylthiadiazolamide of acetylaminohexanoic acid
bioavailability
hplc-ms/ms
url https://www.pharmacokinetica.ru/jour/article/view/53
work_keys_str_mv AT asmalygin assessmentofbioavailabilityofethylthiadiazolylamideofacetylaminohexanoicacidbyintragastricadministrationinrabbits
AT nspopov assessmentofbioavailabilityofethylthiadiazolylamideofacetylaminohexanoicacidbyintragastricadministrationinrabbits
AT mademidova assessmentofbioavailabilityofethylthiadiazolylamideofacetylaminohexanoicacidbyintragastricadministrationinrabbits
AT sbmarasanov assessmentofbioavailabilityofethylthiadiazolylamideofacetylaminohexanoicacidbyintragastricadministrationinrabbits