In situ study of the effect of naringin, talinolol and protein-energy undernutrition on intestinal absorption of saquinavir in rats.

Abstract

To study the potential interactions of naringin (NAR), talinolol (TAL) and protein-energy undernutrition (PEU) in the absorption process of saquinavir (SQV), perfusion experiments were performed in the small intestine of rats at different SQV concentrations. The results obtained demonstrated that SQV intestinal absorption was described by simultaneous passive diffusion (k(dif) = 3.44 hr) and saturable absorption (V(ma) = 127.31 μM/hr; K(ma) = 10.50 μM) together with a capacity-limited efflux (V(ms) = 270.53 μM/hr; K(ms) = 23.44 μM). The competitive inhibition constants of NAR on the SQV input and efflux processes were [IC50](a) = 3.98 μM and [IC50](s) = 5.00 μM, respectively. NAR significantly decreased (23-29%; p < 0.05) or kept unaltered the absorption rate constant (k(a) ) of SQV in function of the concentration of both compounds administered. Finally, SQV k(a) significantly increased in PEU status (around 1.8 times) when the drug was perfused either in the presence (p < 0.05) or in the absence (p < 0.01) of NAR. The variations of SQV k(a) when the antiretroviral drug is co-administered with NAR and/or TAL reinforce their interaction in the absorptive process. Malnutrition may result in altered SQV absorption, and further studies are strongly recommended to analyse the impact of this finding on the pharmacokinetic drug profile.

• Authors: Ana Catalán-Latorre, Amparo Nácher, Virginia Merino, Nicolás Víctor Jiménez-Torres, Matilde Merino-Sanjuán
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 109 Issue 4 Pg. 245-52 (Oct 2011) ISSN: 1742-7843 [Electronic] England
• PMID: 21535410 (Publication Type: Journal Article)
• Copyright: © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Chemical References

• Flavanones
• HIV Protease Inhibitors
• Propanolamines
• talinolol
• Saquinavir
• naringin

Topics

• Administration, Oral
• Animals
• Drug Antagonism
• Flavanones (pharmacokinetics)
• HIV Protease Inhibitors (pharmacokinetics)
• Intestinal Absorption (drug effects, physiology)
• Male
• Propanolamines (pharmacokinetics)
• Protein-Energy Malnutrition (metabolism)
• Rats
• Rats, Wistar
• Saquinavir (pharmacokinetics)