@conference{
author = "Bošković, Jelena and Marković, Jelena and Dobričić, Vladimir and Čudina, Olivera",
year = "2018",
abstract = "Amidi ili estri kortienske kiseline metilprednizolona predstavljaju potencijalne
soft glukokortikoide sa manje izraženim neželjenim efektima u odnosu na
konvencionalne glukokortikoide. Retencija i permeabilnost su važne osobine soft
glukokortikoida za primenu na kožu koje mogu značajno uticati na njihovu aktivnost i
pojavu neželjenih efekata. Jedna od in vitro metoda koja se najčešće koristi za procenu
ovih osobina je PAMPA (Parallel Artificial Membrane Permeability Assay). Cilj ovog
rada je procena permeabilnosti i retencije u koži pet amida (MPMA, MPMAB, MPMAIB,
MPMGB i MPPA) i jednog tioestra (MPEMP) kortienske kiseline metilprednizolona
primenom PAMPA testa.
Procena permeabilnosti i retencije u koži izvršena je na hidrofobnoj Millipore
PVDF PAMPA mikrotitarskoj ploči sa 96 odeljaka. Praćena je difuzija ispitivanih
jedinjenja kroz membranu koju čine 70 % silikonsko ulje i 30 % izopropilmiristat.
Koncentracije u polaznim rastvorima, donorskim i akceptorskim odeljcima određene su
primenom LC‐MS/MS metode.
Primenom PAMPA testa određeni su koeficijenti permeabilnosti (logPe) i
retencije (R). Vrednosti logPe su u opsegu od ‐6,81 do ‐5,09, dok su vrednosti R u
opsegu 1,52 ‐ 65,25. Jedinjenje sa najnižom vrednošću logPe je MPMGB, dok su za
MPEMP određene najviše vrednosti parametara logPe i R, te se od ovog derivata mogu
očekivati najveća permeabilnost i retencija u koži.
Permeabilnost i retencija u koži pet amida (MPMA, MPMAB, MPMAIB, MPMGB i
MPPA) i jednog tioestra (MPEMP) kortienske kiseline metilprednizolona procenjeni su
primenom PAMPA testa. Najviše vrednosti parametara logPe i R su dobijene za MPEMP,
te se ovaj derivat izdvaja kao najpovoljniji za primenu na kožu., Amides or esters of methylprednisolone‐derived cortienic acid are potential soft glucocorticoids with fewer side effects in comparison to traditional glucocorticoids. Retention and permeability are important properties of soft glucocorticoids for local skin application which could significantly influence their activity and occurrence of side effects. PAMPA (Parallel Artificial Membrane Permeability Assay) is one of the mostly used in vitro methods for the estimation of these properties. The aim of this study was estimation of skin permeability and retention of five amides (MPMA, MPMAB, MPMAIB, MPMGB and MPPA) and one thioester (MPEMP) of metilprednisolone ‐ derived cortienic acid using PAMPA. Estimation of skin permeability and retention was performed on hydrophobic Millipore PVDF PAMPA microtiter 96‐well plate. Diffusion of tested compounds through membrane, consisting of 70% silicon oil and 30% isopropyl myristate, was tested. Concentrations in starting solutions, as well as in donor and acceptor compartments were determined using LC‐MS/MS method. PAMPA permeability coefficients (logPe) and retention (R) were determined. logPe values ranged from ‐6.81 to ‐5.09, whereas R values ranged from 1.52 to 65.25. Derivative with the lowest value of logPe was MPMGB, whereas the highest values of logPe and R were determined for MPEMP. Therefore, highest skin permeability and retention could be expected from MPEMP. Skin permeability and retention of five amides (MPMA, MPMAB, MPMAIB, MPMGB and MPPA) and one thioester (MPEMP) of metilprednisolone ‐ derived cortienic acid was estimated by use of PAMPA. The highest values of logPe and R were calculated for MPEMP, which could be considered the best candidate for skin application.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Primena PAMPA testa u proceni permeabilnosti i retencije u koži derivata kortienske kiseline metilprednizolona kao potencijalnih soft glukokortikoida, The use of PAMPA for skin permeability and retention evaluation of metilprednisolone - derived cortienic acid derivatives as potential soft glucocorticoids",
volume = "68",
number = "3",
pages = "387-388",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5454"
}
