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

Abstract

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/RF-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.

Modeling Kinetics of Subcellular Disposition of Chemicals

“…A size exclusion limit of 250 Da was suggested for intestinal absorption by the paracellular route, giving rise to further nonlinearities in the rate-lipophilicity dependence. 2238,[2289][2290][2291] Similar considerations led to the formulation of the permeability model consisting of a molecular-weightdependent set of sigmoids on lipophilicity. 2292,2293 Sigmoidal dependences were found for the measures of hydrogen-bonding ability of molecules, the sum of the hydrogen-bond donor and acceptor fragment values, 2294 the sum of the molecular hydrogen-bonding potentials, 2295 and the sum of hydrogen-bond donors and acceptors.…”

“…The models explained the experimentally observed pH shift, as the consequence of the diffusion in unstirred layers. A size exclusion limit of 250 Da was suggested for intestinal absorption by the paracellular route, giving rise to further nonlinearities in the rate−lipophilicity dependence. ,– Similar considerations led to the formulation of the permeability model consisting of a molecular-weight-dependent set of sigmoids on lipophilicity. , …”

Non-linear Intestinal Absorption Kinetics of Cefadroxil in the Rat

“…A mixture of methanol and aqueous phosphate buffer I / 15 M, of pH 2.8 in proportions 10: 90 (v/v) was used as elution fluid at a flow rate of 1 mL min-I, at room temperature (20°C). After study of a variety of literature recommended mobile phases the solvent mixture was selected as being the most suitable to avoid interferences due to endogenous contaminants, presumably histaminoid substances (Casabo et al 1987).…”

Intrinsic Absolute Bioavailability Prediction in Rats Based on In Situ Absorption Rate Constants and/or In Vitro Partition Coefficients: 6‐Fluoroquinolones

“…In the present report, a similar Equation is used as a tentative approach to predicting the intrinsic (i.e., from a solution) extent of bioavailability, F , of a drug or drug candidate belonging to a series by means of a simple determination of its in situ intrinsic intestinal absorption rate constant ( k a ) in anesthetized rats 5–8. The working expression can be: in which T is the absorbing time.…”