Dasatinib was identified as a potent orally administered Src/Abl kinase inhibitor with excellent antiproliferative activity against Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. The low bioavailability of Dasatinib may be due to both incomplete oral absorption and first-pass metabolism. A prodrug, JLTN, was synthesized to minimize the first-pass effect of Dasat...

Even after a century, heparin is still the most effective anticoagulant available with few side effects. The poor oral absorption of heparins triggered the search for strategies to achieve oral bioavailability since this route has evident advantages over parenteral administration. Several approaches emerged, such as conjugation of heparins with bile acids and lipids, formulation with penetratio...

Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring in vivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use o...

Oral Bioavailability is the rate and extent to which an active drug substance is absorbed and becomes available to the general circulation. A computational model for the prediction of oral bioavailability is a vital initial step in the drug discovery. It is decisive for selecting the promising compounds for the next level optimizations and recognition for the clinical trials. In the present inv...

The pharmacokinetics and oral bioavailability of (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethylphenyl]thiazol-2-yl]benzenesulfonamide (1), a 3-pyridyl thiazole benzenesulfonamide beta3-adrenergic receptor agonist, were investigated in rats, dogs, and monkeys. Systemic clearance was higher in rats (approximately 30 ml/min/kg) than in dogs and monkeys (...

A novel in vitro Caco-2 hepatocyte hybrid system was set up and tested for its ability to predict the oral bioavailability (F) in humans of 24 randomly chosen marketed drugs. Caco-2 cells were cultured on the transwell filters to form tight junctions. Pooled cryopreserved human hepatocytes were placed in the basolateral receiver compartment. To evaluate the permeability and hepatic first pass i...

This open-label, single-period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130-mg evacetrapib oral dose and 4-h intravenous (IV) infusion of 175 µg [(13) C8 ]-evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [(13) C8 ]-evacetrapib using high-performance liquid chromatography/...

The aim of the present investigation was to compare pharmacokinetic profile (bioavailability) of aceclofenac by transdermal and oral application. Nanoemulsion, nanoemulsion gel and marketed tablet (Aceclofar®) were subjected to pharmacokinetic (bioavailability) studies on Wistar male rats. Several pharmacokinetic parameters like Cmax, tmax, AUC0→t, AUC0→α, Ke, and T1/2 were determined for each ...

A sensitive and specific HPLC method with internal standard was developed and validated to determine vitexin-2”-O-rhamnoside (VOR) in rat plasma after oral and intravenous administration. VOR presented a very low bioavailability, the P-glycoprotein inhibitors such as verapamil and ketoconazole and absorption promoting agent, i.e. bile salts were therefore respectively applied to investigate the...