Synthesis of a novel adamantyl nitroxide derivative with potent anti-hepatoma activity in vitro and in vivo.

In this study, a novel adamantyl nitroxide derivative was synthesized and its antitumor activities in vitro and in vivo were investigated. The adamantyl nitroxide derivative 4 displayed a potent anticancer activity against all the tested human hepatoma cells, especially with IC50 of 68.1 μM in Bel-7404 cells, compared to the positive control 5-FU (IC50=607.

Effect of food on the pharmacokinetics of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid, in healthy subjects.

Objective: The objective of this study was to evaluate the pharmacokinetic parameters of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), following a single oral dose of 900 mg in healthy subjects under fed and fasting conditions.

Methods: The study participants (n=12) were randomized to receive one 900 mg triflusal capsule in a fasting condition (no food for 12 hours) or a fed condition (after a high-fat meal); after a 2-week washout period, participants received the same dose of triflusal capsule under the converse condition. Pharmacokinetic parameters were calculated using WinNonlin 6.

The effect of lansoprazole, an OCT inhibitor, on metformin pharmacokinetics in healthy subjects.

Purpose: Gastro-esophageal reflux disease is common in patients with type 2 diabetes. A common treatment is the co-administration of proton-pump inhibitors (PPIs) and metformin. To date, however, the effects of co-administration of PPIs, which inhibit organic cation transporter (OCT) activity, on the action of metformin (a well-known substrate of OCTs) have not been clearly demonstrated.

Impact on L-carnitine Homeostasis of Short-term Treatment with the Pivalate Prodrug Tenofovir Dipivoxil.

Pivalate-generating prodrugs have been suggested to cause clinically significant hypocarnitinaemia. Tenofovir dipivoxil, a novel ester prodrug of tenofovir, can be used for treatment for hepatitis B and HIV infection and it was necessary to evaluate the effect of its treatment on carnitine homeostasis. We sought to investigate the effect of Class 1 drug tenofovir dipivoxil on endogenous L-carnitine level during a 72-hr test in healthy Chinese volunteers and to establish a suitable dose of L-carnitine nutritional supplement for patients who were administered short-term tenofovir dipivoxil tablets for treatment for hepatitis B and herpes simplex virus infection.

Effects of amlodipine on the oral bioavailability of cephalexin and cefuroxime axetil in healthy volunteers.

In this study, the authors compared the effects of amlodipine (AML) on the bioavailability of cephalexin (LEX) and cefuroxime axetil (CXM). Twenty-four healthy men were randomized to 4 treatments according to a crossover design with a 14-day washout. After an overnight fast, they were administered orally LEX 500 mg alone, LEX 500 mg 2 hours after oral administration of AML 5 mg, CXM 500 mg alone, and CXM 500 mg 2 hours after oral administration of AML 5 mg.

High-performance liquid chromatographic analysis of felotaxel, a novel anti-cancer drug, in rat plasma and in human plasma and urine.

A high-performance liquid chromatographic method was developed for the determination of a new derivative of docetaxel, felotaxel, in rat plasma and human plasma and urine. The separation of felotaxel was performed on a Dikma C18 column with 0.2% formic acid and acetonitrile (50:50) as the mobile phase.

In vitro assessment of cytochrome P450 inhibition and induction potential of felotaxel (SHR110008).

The purpose of this study was to assess the potential inhibitory and inductive effects of felotaxel on cytochrome P450 isozymes in vitro. The inhibitory effects of felotaxel on various CYP isozymes were determined in human liver microsomes. In addition, the ability of felotaxel to induce CYP enzymes in cultured human hepatocytes was evaluated.

Application of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to the pharmacokinetics, tissue distribution and excretion studies of felotaxel (SHR110008) in tumor-bearing mice.

Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new effective taxane with greater anticancer activity and less toxicity than docetaxel. Pharmacokinetic studies in animal models are the important components in clinical development of this agent. In this study, a rapid and sensitive analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of felotaxel in tumor-bearing mice plasma, urine, feces and tissues (brain, heart, liver, lung and kidney and tumor).

Preclinical pharmacokinetic analysis of felotaxel (SHR110008), a novel derivative of docetaxel, in rats and its protein binding ability in vitro.

Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new taxane with potent antitumor effects. The purpose of this research was to evaluate the pharmacokinetic profiles of felotaxel in rats and the protein binding in plasma. Data were collated from several preclinical investigations, where the plasma pharmacokinetics, tissue distribution and excretion of felotaxel were assessed after a single intravenous (i.

The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin.

Aims: To investigate the effect of zinc sulfate on pharmacokinetics of cephalexin when administered concurrently or at strategically spaced dosing times designed to avoid the potential interaction in healthy volunteers.

Methods: In this study, all subjects (n= 12) were randomized to receive the following four treatments, separated by a wash-out period of 7 days: cephalexin 500mg alone, concomitantly with zinc 250mg, 3h after zinc 250mg or 3h before zinc 250mg.

Results: All subjects completed the study safely.

Neuroprotective effect of osthole on MPP+-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production.

Background: The 1-methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it causes a severe Parkinson's disease-like syndrome accompanied by increased levels of intracellular reactive oxygen species (ROS) and apoptotic death. In the present study, we investigated the protective effects of osthole, a coumarin compound extracted from the plant-derived medicine Cnidium monnieri, on MPP(+)-induced cytotoxicity in cultured rat adrenal pheochromocytoma (PC12) cells.

Methods: PC12 cells were treated with MPP(+) 2h after treated with different concentrations of osthole.

1-Methyl-1,2,3,4-tetra-hydro-carbolin-2-ium-3-carboxyl-ate.

The title compound, C(13)H(14)N(2)O(2), is a natural product isolated from Cicer arietinum L. (chickpea). The benzene ring and pyrrole rings display planar conformations and the piperidine ring has a half-chair conformation.