Lipophilicity of some GABAergic phenols and related compounds determined by HPLC and partition coefficients in different systems

Effects of Gabaergic Phenols on Phospholipid Bilayers as Evaluated by <sup>1</sup>H-NMR

“…In the glycerol backbone region (peaks I, J, K) hydrogens have intermediate, smoothly higher mobility than hydrogen at carbons α and β of the acyl chain (peaks E, C) due to the high molecular packing of that region. The profile of acyl chain EPC hydrogens (peaks B to A) dynamics is in agreement with that described by other authors and obtained through 13 [23,24] showing increased mobility towards the terminal methyl group-peak A.…”

“…coefficient determined in other comparable systems reported before [13] with a hydrophobic profile of: chlorotymol ≥ propofol > carvacrol ≥ thymol > eugenol. 1 H-NMR spectra (600 MHz) of each compound, of EPC unilamellar vesicles and of samples containing vesicles in the presence of each compound, at a 1:3 (phenol:lipid) molar ratio, were collected.…”

“…The volume of the membrane phase, V m , was calculated assuming a lipid density of 1 g/mL [16]. The amount of each phenolic compound bound to the lipid phase was optically determined at their corresponding wavelengths of maximal absorption between 270 and 282 nm [13] after ultra-centrifugation at 120,000 × g for 2 h, by subtracting the supernatant concentration from the total drug concentration measured before phase mixing.…”

“…The results obtained, based on the octanol-water partition coefficient (logP o/w), retention data in high performance liquid chromatography (HPLC) using C18 and immobilized artificial membrane (IAM) columns at different temperatures, and partition coefficients determined with phospholipid liposomes, demonstrated the high capacity of all the compounds to interact with membrane phases [13]. In addition, by using Langmuir films and epifluorescence images, we described that all the compounds were able to diffuse into the membrane, placing themselves between phospholipid molecules probably at the head-group region [14].…”

Application of a Physiologically Based Pharmacokinetic Model to Assess Propofol Hepatic and Renal Glucuronidation in Isolation: Utility of In Vitro and In Vivo Data

“…Assumptions Applied to the Propofol PBPK Model. The following assumptions were made: 1) there is no active uptake or efflux of propofol in any tissue and therefore tissue distribution/elimination is perfusion rate limited; this assumption seems justifiable because, together with the high lipophilicity of propofol (Reiner et al, 2009), there is a lack of in vitro or in vivo data suggesting that propofol is a substrate of transporters; 2) propofol does not affect the cardiac output (Grounds et al, 1985;Price et al, 1992); and 3) the volume of distribution at steady state (V ss ) for the anhepatic patients was not expected to be markedly different from that in healthy subjects. This is supported by a number of studies where changes in V ss for patients with varying grades of liver cirrhosis were not apparent in comparison with patients with healthy livers (mean values ranging from 202 to 637 l in subjects with mild liver cirrhosis) (Servin et al, 1988a(Servin et al, , b, 1990.…”