Pharmacokinetics and Enterohepatic Circulation of 2-(Quinoline-8-carboxamido)benzoic Acid (2-QBA) in Mice.

The quinoline alkaloid 2-(quinoline-8-carboxamido)benzoic acid (2-QBA), which is isolated from sp. SCSIO06786, a deep sea-derived fungus, has been suggested as a therapeutic candidate for the treatment of Parkinson's disease. We developed an analytical method for 2-QBA using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) in mouse plasma, in which a protein precipitation method for the sample preparation of 2-QBA in mouse plasma was used due to its simplicity and good extraction recovery rates (80.

In Vitro Metabolism and Transport Characteristics of Zastaprazan.

Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this compound in hepatocyte suspension and when 18 phase I metabolites and 5 phase II metabolites [i.e.

Carboxymethyl cellulose-based rotigotine nanocrystals-loaded hydrogel for increased transdermal delivery with alleviated skin irritation.

Transdermal rotigotine (RTG) therapy is prescribed to manage Parkinson's disease (Neupro® patch). However, its use is suffered from application site reactions. Herein, drug nanocrystalline suspension (NS)-loaded hydrogel (NS-HG) employing polysaccharides simultaneously as suspending agent and hydrogel matrix was constructed for transdermal delivery, with alleviated skin irritation.

Effect of dietary extract on growth performance of growing pigs and absorption rate of quercetin in blood.

This study was done to investigate the effects of the incorporation of extracts (AJE) in diet on the production parameters of growing pigs. Exp 1: Total, 105 crossbred pigs (average body weight: 24.47 ± 2.

Recent Advances in Doxorubicin Formulation to Enhance Pharmacokinetics and Tumor Targeting.

Doxorubicin (DOX), a widely used drug in cancer chemotherapy, induces cell death via multiple intracellular interactions, generating reactive oxygen species and DNA-adducted configurations that induce apoptosis, topoisomerase II inhibition, and histone eviction. Despite its wide therapeutic efficacy in solid tumors, DOX often induces drug resistance and cardiotoxicity. It shows limited intestinal absorption because of low paracellular permeability and P-glycoprotein (P-gp)-mediated efflux.

Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer's disease.

Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer's disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery.

Concomitant Administration of Red Ginseng Extract with Lactic Acid Bacteria Increases the Plasma Concentration of Deglycosylated Ginsenosides in Healthy Human Subjects.

With the increased frequency of red ginseng extract (RGE) and lactic acid bacteria (LAB) co-administration, we aimed to investigate the interactions between RGE and LAB with regard to in vitro and in vivo deglycosylation metabolism and the pharmacokinetics of ginsenosides. As a proof-of-concept study, five healthy humans were administered RGE (104.1 mg of total ginsenosides/day) with or without co-administration of LAB (2 g, 1 billion CFU/day) for 2 weeks, and the plasma concentrations of ginsenosides in human plasma were monitored.

Simultaneous Analysis of a Combination of Anti-Hypertensive Drugs, Fimasartan, Amlodipine, and Hydrochlorothiazide, in Rats Using LC-MS/MS and Subsequent Application to Pharmacokinetic Drug Interaction with Red Ginseng Extract.

Fimasartan, amlodipine, and hydrochlorothiazide are commonly used in combination therapies as antihypertensive drugs. This study aimed to develop and validate an analytical method for fimasartan, its active and major metabolite fimasartan-amide, amlodipine, and hydrochlorothiazide in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The standard calibration curves for fimasartan (1−500 ng/mL), its active and major metabolite fimasartan-amide (0.

Enhanced bioavailability and hepatoprotective effect of silymarin by preparing silymarin-loaded solid dispersion formulation using freeze-drying method.

This study aimed to develop a solid dispersion formulation of silymarin (Silymarin-SD) using freeze-drying method to enhance its oral bioavailability (BA) by inhibiting the intestinal first-pass effect and increasing its solubility and permeability. Silymarin-SD formulation (i.e.

Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice and Rats.

This study investigated the pharmacokinetics and tissue distribution of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor that is currently in phase three clinical trials. Enavogliflozin showed dose-proportional pharmacokinetics following intravenous and oral administration (doses of 0.3, 1, and 3 mg/kg) in both mice and rats.

Enhancing Dissolution and Oral Bioavailability of Ursodeoxycholic Acid with a Spray-Dried pH-Modified Extended Release Formulation.

Ursodeoxycholate (UDCA) has low oral bioavailability and pH-dependent solubility and permeability. Thus, we developed a pH-modified extended-release formulation of UDCA using NaCO as the alkalizing agent and hydroxypropyl methylcellulose (HPMC) as the release-modifying agent. The optimized pH-modified controlled-release UDCA formulation, with the UDCA:HPMC:NaCO ratio of 200:600:150 (//), was prepared using a spray-drying method.

Dietary inclusion of Achyranthes japonica extract to corn-soybean meal-wheat-based diet on the growth performance, nutrient digestibility, cecal microflora, excreta noxious gas emission, and meat quality of broiler chickens.

This research was conducted to determine the effects Achyranthes japonica extract (AJE) supplementation to corn-soybean meal-wheat-based diet on the growth performance, nutrient digestibility, cecal microflora, excreta noxious gas emission, and meat quality of broiler chickens. A total of 432 one-day-old male Ross 308 broiler chickens, having initial body weight (IBW) of 41.11 ± 1.

Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer's disease mice.

Alzheimer's disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment.

Effect of Lactic Acid Bacteria on the Pharmacokinetics and Metabolism of Ginsenosides in Mice.

This study aims to investigate the effect of lactic acid bacteria (LAB) on in vitro and in vivo metabolism and the pharmacokinetics of ginsenosides in mice. When the in vitro fermentation test of RGE with LAB was carried out, protopanaxadiol (PPD) and protopanaxadiol (PPD), which are final metabolites of ginsenosides but not contained in RGE, were greatly increased. Compound K (CK), ginsenoside Rh1 (GRh1), and GRg3 also increased by about 30%.

Improved Hygroscopicity and Bioavailability of Solid Dispersion of Red Ginseng Extract with Silicon Dioxide.

This study aims to develop a powder formulation for the Korean red ginseng extract (RGE) and to evaluate its in vitro and in vivo formulation characteristics. The solid dispersion of RGE was prepared with hydrophilic carriers using a freeze-drying method. After conducting the water sorption-desorption isothermogram (relative humidity between 30 and 70% RH), differential scanning calorimetry thermal behavior, dissolution test, and intestinal permeation study, a solid dispersion formulation of RGE and silicon dioxide (RGE-SiO) was selected.

Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity.

We evaluated the bioavailability, liver distribution, and efficacy of silymarin-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) solid dispersion (silymarin-SD) in rats with acetaminophen-induced hepatotoxicity (APAP) compared with silymarin alone. The solubility of silybin, the major and active component of silymarin, in the silymarin-SD group increased 23-fold compared with the silymarin group. The absorptive permeability of silybin increased by 4.

Pharmacokinetic Drug-Drug Interactions and Herb-Drug Interactions.

Due to the growing use of herbal supplementation-ease of taking herbal supplements with therapeutics drugs (i [...

Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid.

We investigated the involvement of drug transporters in the pharmacokinetics of rosmarinic acid in rats as well as the transporter-mediated drug interaction potential of rosmarinic acid in HEK293 cells overexpressing clinically important solute carrier transporters and also in rats. Intravenously injected rosmarinic acid showed bi-exponential decay and unchanged rosmarinic acid was mainly eliminated by urinary excretion, suggesting the involvement of transporters in its renal excretion. Rosmarinic acid showed organic anion transporter (OAT)1-mediated active transport with a K of 26.

A Glycosylated Prodrug to Attenuate Neuroinflammation and Improve Cognitive Deficits in Alzheimer's Disease Transgenic Mice.

We report a prodrug, , to overcome the shortcomings of an anti-neuroinflammatory molecule, -diacetyl--phenylenediamine (), in biological applicability for potential therapeutic applications. We suspect that can release through endogenous enzymatic bioconversion. Consequently, exhibits in vivo efficacies in alleviating neuroinflammation, reducing amyloid-β aggregate accumulation, and improving cognitive function in Alzheimer's disease transgenic mice.

Pharmacokinetics of ginsenosides following repeated oral administration of red ginseng extract significantly differ between species of experimental animals.

We aimed to investigate ginsenoside pharmacokinetics in mice and rats following the repeated oral administration of red ginseng extract (RGE) (2 g/kg/day for 7 days). In mouse plasma, seven protopanaxadiol (PPD)-type ginsenosides (20(S)-ginsenoside Rb1, Rb2, Rc, Rd, Rg3, 20(S)-compound K, and 20(S)-PPD) and one protopanaxatriol (PPT)-type 20(S)-ginsenoside Re were detected, whereas 20(S)-ginsenoside Rb1, Rb2, Rc, Rd, 20(S)-PPD, and 20(S)-PPT were detected in rat plasma. The tetra- or tri-glycosylated PPD-type ginsenosides Rb1, Rb2, Rc, and Rd, high content ginsenosides in RGE, showed high plasma exposure, a short absorption time (T), and a long elimination time (T) among the ginsenosides detected in both species.

The Development and Validation of a Novel "Dual Cocktail" Probe for Cytochrome P450s and Transporter Functions to Evaluate Pharmacokinetic Drug-Drug and Herb-Drug Interactions.

This study was designed to develop and validate a 10 probe drug cocktail named "Dual Cocktail", composed of caffeine (Cyp1a2 in rat and CYP1A2 in human, 1 mg/kg), diclofenac (Cyp2c11 in rat and CYP2C9 in human, 2 mg/kg), omeprazole (Cyp2c11 in rat and CYP2C19 in human, 2 mg/kg), dextromethorphan (Cyp2d2 in rat and CYP2D6 in human, 10 mg/kg), nifedipine (Cyp3a1 in rat and CYP3A4 in human, 0.5 mg/kg), metformin (Oct1/2 in rat and OCT1/2 in human, 0.5 mg/kg), furosemide (Oat1/3 in rat and OAT1/3 in human, 0.

Enhanced Intestinal Absorption and Pharmacokinetic Modulation of Berberine and Its Metabolites through the Inhibition of P-Glycoprotein and Intestinal Metabolism in Rats Using a Berberine Mixed Micelle Formulation.

We aimed to develop a berberine formulation to enhance the intestinal absorption and plasma concentrations of berberine through the inhibition of P-glycoprotein (P-gp)-mediated efflux and the intestinal metabolism of berberine in rats. We used pluronic P85 (P85) and tween 80, which have the potential to inhibit P-gp and cytochrome P450s (i.e.

N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer's disease.

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1.

Comparative Pharmacokinetics and Pharmacodynamics of a Novel Sodium-Glucose Cotransporter 2 Inhibitor, DWP16001, with Dapagliflozin and Ipragliflozin.

Since sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced blood glucose level by inhibiting renal tubular glucose reabsorption mediated by SGLT2, we aimed to investigate the pharmacokinetics and kidney distribution of DWP16001, a novel SGLT2 inhibitor, and to compare these properties with those of dapagliflozin and ipragliflozin, representative SGLT2 inhibitors. The plasma exposure of DWP16001 was comparable with that of ipragliflozin but higher than that of dapagliflozin. DWP16001 showed the highest kidney distribution among three SGLT2 inhibitors when expressed as an area under curve (AUC) ratio of kidney to plasma (85.

Tolerability and pharmacokinetics of ginsenosides Rb1, Rb2, Rc, Rd, and compound K after single or multiple administration of red ginseng extract in human beings.

Background: We investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings.

Methods: Red ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods.