Evidence of a specialized transport mechanism for the intestinal absorption of baclofen

Abstract

Absorption of the spasmolytic drug baclofen in three selected intestinal segments of living anaesthetized rats in situ, is shown to be a specialized transport mechanism obeying Michaelis-Menten kinetics. Equation parameters were calculated through different procedures, whose features are discussed. A computer method based on the integrated form of Michaelis-Menten equation which reproduces the entire time course of drug absorption from the data found in three intestinal perfusion series at different initial concentrations, yielded Vm and Km values of 12.0 mg h-1 and 8.0 mg, respectively, in the mean segment of the small intestine, a rather selective absorption site for baclofen. Lesser but comparable absorption rates were found in the proximal and distal segments of the small intestine, whereas in colon, drug absorption was negligible. Baclofen transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. If these results were extrapolated to humans, they would explain the excellent bioavailability profiles reported for baclofen at normal doses in spite of its physicochemical properties, which do not favour passive diffusion. Based on the same principle, the administration of usual doses at shorter time intervals could be recommended, instead of high, when higher plasma levels at steady-state are needed. On the other hand, more than 8-h sustained-release preparations of baclofen should, probably, be avoided.

Interaction of Taurine on Baclofen Intestinal Absorption: A Nonlinear Mathematical Treatment using Differential Equations to Describe Kinetic Inhibition Models

“…16 Fitting of Models to Data and Statistical Proceduress Absorption Rate MeasurementssAbsorption rate measurements were assessed both for baclofen and for taurine. In a previous paper 11 it was shown that baclofen absorption can be described as a specialized transport mechanism obeying Michaelis-Menten kinetics. Nevertheless, we used the classical first-order equation to measure baclofen intestinal absorption because it gives an accurate description of the absorption profiles within a limited time interval (i.e., from 0 to 30 min), with good correlation coefficients.…”

“…A rat gut in situ preparation, 10 modified as previously reported, [11][12][13] was used. Briefly, a midline incision was made and a fraction of the middle intestine of about 35 cm length (measured 30 cm from the pylorus) was cannulated.…”

Labetalol absorption kinetics: Rat small intestine and colon studies

“…For this purpose antipyrine was selected, since it is known to be only passively absorbed. 11 Therefore, solutions containing antipyrine 133 mM with and without verapamil 7 mM were perfused in the small intestine of the rat.…”

“…These results are acceptable from a biopharmaceutical viewpoint. 12 The analytical technique used for antypirine was previously described 11 and validated.…”

Arbaclofen Placarbil, a Novel R-Baclofen Prodrug: Improved Absorption, Distribution, Metabolism, and Elimination Properties Compared with R-Baclofen

“…The optimal exposure to R-baclofen for the treatment of spasticity or GERD may be a stable therapeutic plasma concentration. Because of limited absorption of baclofen in the large intestine, attempts to develop a sustained release formulation of the drug have not been successful (Merino et al, 1989).…”