The influence of bile salts on the distribution of simvastatin in the octanol/buffer system
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Bile acids and their derivatives as potential modifiers of drug release and pharmacokinetic profilesPavlovic, N.; Golocorbin-Kon, S.; Danic, M.; Stanimirov, B.; Al-Salami, Hani; Stankov, K.; Mikov, M. (2018)Copyright © 2018 Pavlovic, Golocorbin-Kon, Danic, Stanimirov. Bile acids have received considerable interest in the drug delivery research due to their peculiar physicochemical properties and biocompatibility. The main ...
Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes.Mooranian, A.; Zamani, N.; Takechi, R.; Al-Sallami, H.; Mikov, M.; Golocorbin-Kon, S.; Kovacevic, B.; Arfuso, Frank; Al-Salami, H. (2018)INTRODUCTION: The ratio of secondary to primary bile acids changes during Type 1 Diabetes (T1D) development and these effects might be ameliorated by using cholesterol lowering drugs or hydrophilic bile acids. Probucol ...
Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic ß-cell lineMooranian, A.; Negrulj, R.; Arfuso, Frank; Al-Salami, H. (2015)CONTEXT: We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). OBJECTIVE: This study aimed ...