Both patients and physicians prefer the oral route of drug delivery. The gastrointestinal (GI) tract, though, limits the bioavailability of certain therapeutics because of its protease and bacteria-rich environment as well as general pH variability from pH 1 to 7. These extreme environments make oral delivery particularly challenging for the biologic class of therapeutics. Here, we demonstrate ...

Antimalarial 4-pyridones are a novel class of inhibitors of the plasmodial mitochondrial electron transport chain targeting Cytochrome bc1 (complex III). In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form. The strategy of introducing polar hydroxymethyl groups has ...

The pharmacokinetics of chlormethiazole were studied in eight patients with advanced cirrhosis of the liver and in six healthy volunteers after oral and intravenous administration of the drug. In the patients the systemic bioavailability of oral chlormethiazole was increased about tenfold, whereas its elimination was only slightly retarded. The increased bioavailability was clearly due to decre...

Grapefruit juice produces mechanism-based inhibition of intestinal drug metabolism when consumed in normal quantities. This can produce clinically important increases in oral drug bioavailability when coadministered with substrates of cytochrome p450 3A4 (CYP3A4) that undergo high presystemic metabolism. Furanocoumarins such as bergamottin and 6',7'-dihydroxybergamottin have been identified as ...

Baicalin (BA) is a major constituent of Scutellaria baicalensis Georgi, a medicinal herb. Previous pharmacokinetic studies of BA showed its low oral bioavailability. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) to enhance oral bioavailability. BA-LP, composed of BA, Tween(®) 80, Phospholipon(®) 90H, and citric acid at weight ratio of 96/50/96/50, respectively, ...

Previous studies in mice with disrupted mdr1a P-glycoprotein genes have shown that the oral bioavailability of paclitaxel is very low because of the presence of this drug-transporting protein in the intestinal wall. Additional studies with cyclosporin A have shown that this P-glycoprotein-inhibiting agent is able to increase the bioavailability of paclitaxel in mouse models and in patients. How...

Despite the fact that various studies have investigated the clinical relevance of ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy, little has been reported regarding the efficient strategy for improving its oral bioavailability. In this study, we report the formulation of EA-loaded nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as bioavai...

The purpose of this study was twofold. The first aim was to evaluate the oral bioavailability and pharmacokinetics (PKs) of acyclovir in horses after intravenous (i.v.) administration and after oral administration of acyclovir and its prodrug, valacyclovir. Second, we aimed to combine these PK data with pharmacodynamic (PD) information, i.e., 50% effective concentrations (EC(50) values) from in...

BACKGROUND AND AIM The pharmacokinetics of acemetacin, a non-steroidal anti-inflammatory drug which is biotransformed to indomethacin by hepatic first-pass effect, was examined during the necrotic and regeneration phases resulting from acute hepatitis induced by carbon tetrachloride (CCl4). MATERIAL AND METHODS Acute hepatitis was induced by oral CCl4 administration to male Wistar rats. On da...

Nanostructured lipid carriers (NLCs), a lipid based colloidal carrier system, offer many advantages such as increase the solubility, improves the bioavailability and therapeutic efficacy. Incorporation of liquid lipid can improve the drug loading capacity in the NLCs. Valsartan is an antihypertensive drug with low oral bioavailability ranging from 10-35% because of poor solubility and extensive...