A. Martín-Villodre

Studies on the reliability of a bihyperbolic functional absorption model. I. Ring-substituted anilines

The present study reviews and checks the rearranged master lines of the functional bihyperbolic absorption model proposed by Plá-Delfina and Moreno, by examining the correlations between absorption rate constants experimentally found in the small intestine and in the colon of the rat, and two types of partition constants for a series of ring-substituted anilines, of low to medium molecular weight. Evidence is given which demonstrates the reliability of the bihyperbolic equation for the small intestine data, showing the importance of the type of substitution in the absorption rate of compounds; for the colonic data, the collapsed, monohyperbolic form of this equation (i.e., the Wagner-Sedman equilibrium model) applies, independent of the nature and position of the group substituents in the aniline molecule. This means that, as the bihyperbolic model equation predicts, aqueous pore diffusion is a crucial factor, as important as membrane permeation, in absorption in the small intestine, whereas in the colon only this latter route is operative. The perspectives opened by the application of the model to gastrointestinal absorption studies are also discussed.

Non‐linear Intestinal Absorption Kinetics of Cefadroxil in the Rat

Abstract— Absorption of Cefadroxil in a selective intestinal absorption area (the proximal third of the small intestine) of the anaesthetized rat, at seven initial perfusion concentrations, ranging from 0·01 to 10·0 mg mL−1, is shown to be a non‐linear transport mechanism. With the aid of computer‐fitting procedures based on differential and integrated forms of Michaelis‐Menten equation, Vm and Km values of 36·7–37·3 mg h−1 and 12·0–13·0 mg, respectively, were found. The statistical parameters were better than those obtained both for first‐order and for combined Michaelis‐Menten and first‐order kinetics. There is no evidence for substantial passive diffusion processes. The results reported here, together with allometric considerations and literature data analysis, may help to explain some particular non‐linear features of plasma level curves associated with the administration of fairly high oral doses of Cefadroxil to humans.

Consistency of Carbopol 971-P NF gels and influence of soluble and cross-linked PVP.

A study is made of the polymerization process of polyacrylic acid, commercially known as Carbopol 971 NF, assessing its consistency as a function of the degree of neutralization at pH values from 3 to 12, approximately. Percentage concentrations ranging from 0.1 to 1.4% (w/w) were studied. The gels obtained were non-Newtonian, and pseudoplastic. As concentration and pH rise, the consistency of the gels increase to a maximum, which appears between pH 6 and 8, allowing their use as vehicles in bioadhesive formulations for mucosal application. Over the increasing viscosity interval, functions were obtained to indicate the consistency of the gel as a function of pH and concentration. Since the correlation between the theoretical and experimental results is excellent, the equation found can be used to theoretically calculate the working concentration and pH required to secure the necessary consistency for a given vehicle. The addition of soluble polyvinylpyrrolidone (PVP), and cross-linked PVP (PVPP) does not substantially modify the rheological behavior of the gels, thus permitting their addition to usual vehicles.

Studies on the reliability of a bihyperbolic functional absorption model. II. Phenylalkylamines.

Evidence is given that demonstrates the reliability of the bihyperbolic equation, proposed by Plá-Delfina and Moreno, in fitting the correlation between absorption rate constants (ka) found in the small intestine and in the colon of the living anesthetized rat, and partition constants (1/R.F−1), for a series of phenylalkylamines, a group of compounds which differ largely from others which have been tested. Emphasis is laid on the nonexistence of an optimum of lipophilicity for intestinal absorption/partition correlation: This feature makes inapplicable the probabilistic approaches to the reported data.

Absorption-partition relationships for true homologous series of xenobiotics as a possible approach to study mechanisms of surfactants in absorption. III. Aromatic amines and cationic surfactants

Abstract The previously proposed approaches for interpreting and quantifying the mechanisms elicited by nonionic surfactants on the intestinal and colonic absorption of 4-alkylanilines are extended here to the cationic surfactants dodecyltrimethylammonium bromide and tetradecyltrimethylammonium bromide. The effects of the cationics run parallel to those observed for nonionics and the only modification observed is a more effective membrane polarity increase, possibly inherent to their cationic nature. Therefore, the mechanisms involved in xenobiotic absorption modifications seem to be characteristic of the surfactants and independent of their ionization properties.