Lipoidal membrane

The polyisoprenoids dolichol (Figure 14-20 and Chapter 47) and ubiquinone (Figure 12-5) are formed from farnesyl diphosphate by the further addition of up to 16 (dolichol) or 3-7 (ubiquinone) isopentenyl diphosphate residues, respectively. Some GTP-binding proteins in the cell membrane are prenylated with farnesyl or geranylgeranyl (20 carbon) residues. Protein prenylation is believed to facilitate the anchoring of proteins into lipoid membranes and may also be involved in protein-protein interactions and membrane-associated protein trafficking. 

Dibbern HW, Scholz GH (1969) Resorption model experiments with artificial lipoid membranes. 3. Model experiments for gastroenteral resorption. Arzneimittelforschung 19 1140-1145... 

P. Green and J. Hadgraft, Facilitated transfer of cationic drugs across a lipoidal membrane by oleic acid and lauric acid, Int. J. Pharm. 37 251-255 (1987). 

These compounds are able to diffuse through both the membrane and aqueous pores and/or tight junctions. The global absorption rate constant is described by the sum of two absorption rate values which represent two different pathways the penetration into the lipoidal membrane, and across the aqueous pores. B, I , a, and o are constants that depend on the experimental technique used to obtain the absorption rate constants, P is the lipophilicity parameter, and km and kp are the asymptotic values for the membrane and the paracellular way, respectively. For compounds with a molecular weight higher than 250 Da the contribution of the aqueous pathway is negligible, collapsing the equation to the one hyperbola model already described for colon. 

A bilinear equation applies in this special situation where phospholipid and glyco-calyx layers preceed the lipoidal membrane. As in colon and small intestine there... 

For a number of years the existence of a porous or polar pathway through the stratum comeum, in parallel with the lipoidal pathway, has been hypothesized. Although there has been some criticism of this concept, it is our belief that the root of the lack of a common consensus among scientists in the field can be attributed largely to the limited number of systematic studies in the literature that directly address the issue of the diffusion of polar and ionic permeants across skin. Based upon recent studies that have focused upon this aspect of transdermal diffusion, the existence of a porous permeation pathway through HEM is clear (Hatanaka et al., 1993, 1994 Peck et al., 1993, 1994, 1995). At this point, we have made no attempt to correlate the findings from our studies with specific structural properties of the HEM. In some cases, authors have implicated shunt routes such as hair follicles and sweat ducts to account for permeation data not consistent with the concept of lipoidal membrane permeation (Cornwell and Barry, 1993 Scheuplein and Blank, 1971). Under ionto-phoretic conditions, such shunt routes have been shown to contribute to current conduction (Cullander and Guy, 1991 Scott et al., 1993). When efforts have been made to estimate the effective Rp of skin samples under iontophoretic conditions (Ruddy and Hadzija, 1992), osmotic conditions (Hatanaka et al.,... 

The lipid-aqueous partition coefficient of a drug molecule affects its absorption by passive diffusion. In general, octanol/pH 7.4 buffer partition coefficients in the 1-2 pH range are sufficient for absorption across lipoidal membranes. However, the absence of a strict relationship between the partition coefficient of a molecule and its ability to be absorbed is due to the complex nature of the absorption process. Absorption across membranes can be affected by several diverse factors that may include the ionic and/or polar characteristics of the drug and/or membrane as well as the site and capacity of carrier-mediated absorption or efflux systems. 

Pl is the permeability coefficient of the lipoidal membrane Pp is the permeability coefficient of the aqueous pore Xs is the fraction of unionized species is the permeability coefficient of the lipoidal membrane of neutally charged species P, Pp is the permeability coefficient of aqueous pore of positively and negatively charged species, respectively Xf, X, X is the fraction of neutrally, positively, and negatively charged species at the membrane surface, respectively is the permeability coefficient of the membrane for active transport Tlnax is the maximum flux for active transport is the Michaelis constant for active transport. 

Perez-Buendia MD, Gomez-Perez B, Pla-Delfina JM. Permeation mechanisms through artificial lipoidal membranes and effects of synthetic surfactants on xenobiotic permeability. Arzneimittelforschung 1993 Jul 43(7) 789 - 794. 

Many studies show that divalent cations promote membrane fusion (27, 28, 29) and thereby may initiate attachment of granules to the insides of plasma membranes during secretion. Actually these ideas (i.e. enzyme activation and fusion of lipoid membranes by calcium), are not mutually exclusive since it is possible that calcium initiates more than one intracellular change to trigger the secretory process. 

Cyanide may interact with proteins in other ways by forming hydrogen bonds or salt bridges with appropriate sites on protein molecnles. Cyanide in lipoid membranes or bonnd to protein may be in equilibrinm with free CN in biological flnids. 

Articaine [4-methyl-3-(2-propylaminopropionamido) thiophene-2-carboxylic acid methyl ester hydrochloride] has been widely used in dentistry since its approval by the U.S. FDA in the year 2000 because of its quick onset and short duration of action. The structure of articaine differs from those of all other amino amide-type local anesthetics in that it contains a thiophene ring instead of a benzene ring and a carbomethoxy group. This renders the molecule more lipophilic and, thus, easier to cross any lipoidal membranes. 

When solid particles are in the GI tract, a saturated layer of drug solution builds up very quickly on the surfaces of the particles in the liquid immediately surrounding them (called the diffusion layer) (Fig. 8.2). The drug molecules then diffuse through GI content to the lipoidal membrane where diffusion across the... 

Molecules which are strongly bound to serum proteins may be limited to an intravascular volume of distribution even if they are small enough to diffuse through membrane pores or lipid soluble enough to diffuse directly through the lipoidal membrane itself. In some cases, protein binding will not completely eliminate distribution in the extracellular and intravascular compartments since it may only delay diffusion into these compartments. ... 

Four pharmacophores have been identified in CCR5 antagonists 6, namely, a tertiary basic amine, two tail hydrophobes one of which tolerates some polarity, and a (hetero)aryl head (Figure 3.5). In a series of these inhibitors, lipid permeability was very low and strategies to remove the amide function in tail hydrophobe 1 were progressed. Replacement of the secondary amide with a piperidine 7 or azetidine 8 moiety led to the discovery of compounds with increased intrinsic lipoidal membrane permeability and overall an improved in vivo pharmacokinetic profile [7]. 

The active substance should have certain lipophilicity as well. If not, it will not pass the rectal lipoid membranes. On the other hand, a too high lipophilicity causes the active substance to be hardly released from a fatty base. For a systemic effect a good water-soluble active substance is preferred with sufficient lipophilicity at the pH of the rectal fluid to allow passage of the rectal membranes for absorption [8c]. 

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