Glucosamine modulates propranolol pharmacokinetics via intestinal permeability in rats

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Hanadi A Al ShakerAdnan A Badwan

Abstract

Propranolol (PROP) undergoes extensive first-pass metabolism by the liver resulting in a relatively low bioavailability (13-23%); thus, multiple oral doses are required to achieve therapeutic effect. Since some studies have reported that glucosamine (GlcN) can increase the bioavailability of some drugs, therefore, it is aimed to study whether GlcN can change the pharmacokinetic parameters of PROP, thus modulating its bioavailability. When PROP was orally co-administered with GlcN (200mg/kg) to rats, PROP area under curve (AUC) and maximum concentration (Cmax) were significantly decreased by 43% (p<0.01) and 33% (p<0.05), respectively. In line with the in vivo results, in silico simulations confirmed that GlcN decreased rat intestinal effective permeability (Peff) and increased PROP clearance by 50%. However, in situ single pass intestinal perfusion (SPIP) experiments showed that GlcN significantly increased PROP serum levels (p<0.05). Furthermore, GlcN decreased PROP disposition/distribution into cultured hepatocytes in concentration dependent manner. Such change in the interaction pattern between GlcN and PROP might be attributed to the environment of the physiological buffer used in the in vitro experiments (pH7.2) versus the...Continue Reading

Citations

Jul 10, 2019·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·I R DubbelboerH Lennernäs
Apr 17, 2021·International Journal of Pharmaceutics·Klaudia BialekLidia Tajber
Jul 6, 2021·Human & Experimental Toxicology·B Y GhanimN A Qinna

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