The influence of bile salts on the distribution of simvastatin in the octanol/buffer system
Samo za registrovane korisnike
2016
Autori
Danić, MajaPavlović, Nebojša
Stanimirov, Bojan
Vukmirović, Sasa
Nikolić, Katarina
Agbaba, Danica
Mikov, Momir
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Introduction: Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability.Methods: LogD values of SVA and SVL with or without bile salts were measured by liquid-liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes.Results: Statistically significant decrease in both SVA and S...VL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results.Conclusions: Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.
Izvor:
Drug Development and Industrial Pharmacy, 2016, 42, 4, 661-667Izdavač:
- Taylor & Francis Ltd, Abingdon
Finansiranje / projekti:
- Interakcije ksenobiotika i uticaj na sisteme u biomedicini (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41012)
DOI: 10.3109/03639045.2015.1067626
ISSN: 0363-9045
PubMed: 26204349
WoS: 000371810100018
Scopus: 2-s2.0-84964344080
Institucija/grupa
PharmacyTY - JOUR AU - Danić, Maja AU - Pavlović, Nebojša AU - Stanimirov, Bojan AU - Vukmirović, Sasa AU - Nikolić, Katarina AU - Agbaba, Danica AU - Mikov, Momir PY - 2016 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2610 AB - Introduction: Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability.Methods: LogD values of SVA and SVL with or without bile salts were measured by liquid-liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes.Results: Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results.Conclusions: Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients. PB - Taylor & Francis Ltd, Abingdon T2 - Drug Development and Industrial Pharmacy T1 - The influence of bile salts on the distribution of simvastatin in the octanol/buffer system VL - 42 IS - 4 SP - 661 EP - 667 DO - 10.3109/03639045.2015.1067626 ER -
@article{ author = "Danić, Maja and Pavlović, Nebojša and Stanimirov, Bojan and Vukmirović, Sasa and Nikolić, Katarina and Agbaba, Danica and Mikov, Momir", year = "2016", abstract = "Introduction: Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability.Methods: LogD values of SVA and SVL with or without bile salts were measured by liquid-liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes.Results: Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results.Conclusions: Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.", publisher = "Taylor & Francis Ltd, Abingdon", journal = "Drug Development and Industrial Pharmacy", title = "The influence of bile salts on the distribution of simvastatin in the octanol/buffer system", volume = "42", number = "4", pages = "661-667", doi = "10.3109/03639045.2015.1067626" }
Danić, M., Pavlović, N., Stanimirov, B., Vukmirović, S., Nikolić, K., Agbaba, D.,& Mikov, M.. (2016). The influence of bile salts on the distribution of simvastatin in the octanol/buffer system. in Drug Development and Industrial Pharmacy Taylor & Francis Ltd, Abingdon., 42(4), 661-667. https://doi.org/10.3109/03639045.2015.1067626
Danić M, Pavlović N, Stanimirov B, Vukmirović S, Nikolić K, Agbaba D, Mikov M. The influence of bile salts on the distribution of simvastatin in the octanol/buffer system. in Drug Development and Industrial Pharmacy. 2016;42(4):661-667. doi:10.3109/03639045.2015.1067626 .
Danić, Maja, Pavlović, Nebojša, Stanimirov, Bojan, Vukmirović, Sasa, Nikolić, Katarina, Agbaba, Danica, Mikov, Momir, "The influence of bile salts on the distribution of simvastatin in the octanol/buffer system" in Drug Development and Industrial Pharmacy, 42, no. 4 (2016):661-667, https://doi.org/10.3109/03639045.2015.1067626 . .