6533b853fe1ef96bd12acd80
RESEARCH PRODUCT
The influence of active secretion processes on intestinal absorption of salbutamol in the rat.
V.g. CasabóAmparo NácherBelén ValenzuelaA. Martín-villodresubject
Malemedicine.medical_specialtyEnterocytePharmaceutical ScienceIntestinal absorptionchemistry.chemical_compoundInternal medicinemedicineAnimalsAlbuterolATP Binding Cassette Transporter Subfamily B Member 1Rats WistarSodium AzidebiologyDose-Response Relationship DrugChemistryGeneral MedicineAdrenergic beta-AgonistsSmall intestineBioavailabilityRatsEndocrinologymedicine.anatomical_structureIntestinal AbsorptionVerapamilEnzyme inhibitorSalbutamolbiology.proteinVerapamilSodium azideBiotechnologymedicine.drugdescription
Abstract Salbutamol was perfused in the small intestine of rat using a standard rat gut ‘in situ’ preparation: (1) in inhibitor-free solution at seven different concentrations (0.15, 0.29, 1.20, 5.0, 9.0, 13.0 and 18.0 mM); (2) at a 0.29 mM concentration – thought to be close to the allometric dose in man – in the presence of a non-specific enzyme inhibitor, sodium azide (0.3, 3.0 and 6.0 mM); and (3) at 0.29 mM in the presence of a selective secretion inhibitor, verapamil (10.0 and 20.0 mM). In free solution, the mixed-order rate constants, k ′ a , of salbutamol increase as the solute concentration increases until an apparent asymptotic value is reached. This could be due to the saturation of enzymatic systems responsible for the secretion of the drug from the enterocyte to the luminal fluid, a process that could explain the poor absorption of salbutamol. In the presence of sodium azide, the k a values increased about 1.5-fold, whereas in the presence of verapamil they increased two- to three-fold. These results indicate that salbutamol can act as a substrate of an intestinal secretory transport, which probably includes – at least in part – the enzyme P-glycoprotein, since verapamil has been shown to inhibit this enzyme by dose-dependent competition. This leads to a secretion-limited peroral absorption of salbutamol, which contributes to the poor oral bioavailability of the drug. The possible options for improving salbutamol absorption are discussed.
year | journal | country | edition | language |
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2001-07-05 | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V |