Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique
Аутори
Dobričić, VladimirMarodi, Marko
Marković, Bojan
Tomašič, Tihomir
Zidar, Nace
Peterlin Mašič, Lucija
Ilaš, Janez
Kikelj, Danijel
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV
inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution
in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored
[1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl
sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation
were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was
observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model
was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds.
Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and
-4.93, respec...tively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively).
Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13
and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a
reason for lower permeability than expected based on their lipophilicity.
Извор:
Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts, 2020, 41-41Издавач:
- MuTaLig COST ACTION CA15135
Институција/група
PharmacyTY - CONF AU - Dobričić, Vladimir AU - Marodi, Marko AU - Marković, Bojan AU - Tomašič, Tihomir AU - Zidar, Nace AU - Peterlin Mašič, Lucija AU - Ilaš, Janez AU - Kikelj, Danijel PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5460 AB - In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored [1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds. Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and -4.93, respectively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively). Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13 and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a reason for lower permeability than expected based on their lipophilicity. PB - MuTaLig COST ACTION CA15135 C3 - Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts T1 - Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique SP - 41 EP - 41 UR - https://hdl.handle.net/21.15107/rcub_farfar_5460 ER -
@conference{ author = "Dobričić, Vladimir and Marodi, Marko and Marković, Bojan and Tomašič, Tihomir and Zidar, Nace and Peterlin Mašič, Lucija and Ilaš, Janez and Kikelj, Danijel", year = "2020", abstract = "In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored [1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds. Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and -4.93, respectively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively). Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13 and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a reason for lower permeability than expected based on their lipophilicity.", publisher = "MuTaLig COST ACTION CA15135", journal = "Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts", title = "Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique", pages = "41-41", url = "https://hdl.handle.net/21.15107/rcub_farfar_5460" }
Dobričić, V., Marodi, M., Marković, B., Tomašič, T., Zidar, N., Peterlin Mašič, L., Ilaš, J.,& Kikelj, D.. (2020). Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique. in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts MuTaLig COST ACTION CA15135., 41-41. https://hdl.handle.net/21.15107/rcub_farfar_5460
Dobričić V, Marodi M, Marković B, Tomašič T, Zidar N, Peterlin Mašič L, Ilaš J, Kikelj D. Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique. in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts. 2020;:41-41. https://hdl.handle.net/21.15107/rcub_farfar_5460 .
Dobričić, Vladimir, Marodi, Marko, Marković, Bojan, Tomašič, Tihomir, Zidar, Nace, Peterlin Mašič, Lucija, Ilaš, Janez, Kikelj, Danijel, "Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique" in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts (2020):41-41, https://hdl.handle.net/21.15107/rcub_farfar_5460 .