Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2.

The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form.

[Differences of brain pathological changes and cognitive function after bilateral common carotid artery occlusion between Sprague-Dawley and Wistar rats].

The aim of the present study was to investigate the differences of the pathological changes and cognitive function after bilateral common carotid artery occlusion (BCCAO) between Sprague-Dawley (SD) and Wistar rats. Male SD and Wistar rats were randomly divided into 2 groups, respectively: sham operated (S-sham and W-sham) and operated (S-BCCAO and W-BCCAO) groups. The survival rate and the rate of loss of pupillary light reflex (PLR) were observed on day 1, 3, 7, 14 and 28 after the operation, and the light-dark box, Y-maze and odor recognition tests were performed to detect cognitive function on day 28 after the operation.

Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol.

Kaempferol is a natural flavonol that possesses various pharmacological activities, including anti-arthritis effects, yet the underlying mechanisms remain controversial. To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol, collagen-induced arthritis (CIA) mice were treated with kaempferol intragastrically (200 mg · kg · d) and intraperitoneally (20 mg · kg · d). Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index, arthritis index, paw thickness, and inflammatory factors; the bioavailability (1.

[Evaluation of myocardial ischemia rat model based on metabonomic method of small molecule metabolites of plasma and cardiac muscle].

Isoproterenol (ISO)-induced myocardial ischemia animal model has been widely applied to the study of myocardial ischemia and evaluation of drug efficacy. Metabolic profiling of endogenous compounds can make a deep insight into biochemical process of the ISO-induced myocardial ischemia rats. Herein, rats were treated with ISO (2 mg x kg(-1)) for 10 days.

[Metabonomic phenotype of "formula corresponding to pattern types" based on "qi and yin deficiency pattern" of myocardial ischemia rat model].

In order to explore the scientific connotation of "Fangzhengduiying (formula corresponding to pattern types)", "Qiyinliangxuzheng (Qi and Yin deficiency pattern)" of myocardial ischemia rat model and GC-TOF/MS based metabonomic method were used for comparing the effects of Sheng-mai injection, Salvia injection and propranolol in the present study. After data processing and pattern recognition, Sheng-mai injection showed better efficacy than the other two drugs in accordance with not only visual observation from PLS-DA scores plots but also the number of abnormal endogenous compounds restored to the normal level. Further studies showed that Sheng-mai injection could normalize the level of plasma endothelin-1, the index related to cardiovascular diseases and sleep disorders, which verified the results of metabonomics.

[Metabonomic profiling of plasma metabolites in Wistar rats to study the effect of aging by means of GC/TOFMS-based techniques].

The global metabolite profiles of endogenous compounds of Wistar rats from 12 to 20 weeks old were investigated to take deep insight into and get better understanding of the pathogenesis of development and aging. Plasma from Wistar rats at 12, 14, 16, 18, and 20 weeks old were analyzed using GC/TOFMS. Multivariate data analysis was then used to process the metabonomic data which indicated excellent separation between different weeks and showed that the metabolic profiles of the samples changed with age, enabling age-related metabolic trajectories to be visualized.

Metabonomic phenotype and identification of "heart blood stasis obstruction pattern" and "qi and yin deficiency pattern" of myocardial ischemia rat models.

The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition.

Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC-APCI-MS: application of pharmacokinetic study in rats.

20(S)-Protopanaxadiol (PPD), the main metabolite of protopanoxadiol type ginsenosides (e.g. Rg3 and Rh2), is a very promising anti-cancer drug candidate.

Quantitative determination of ophiopogonin d by liquid chromatography/electrospray ionization mass spectrometry and its pharmacokinetics in rat.

A sensitive and rapid liquid chromatography-mass spectrometric method for the determination of ophiopogonin D in rat plasma was developed and validated. Chromatographic separation was performed on a C (18) column using a step gradient program with the mobile phase of 0.5 mmol/L ammonium chloride solution and acetonitrile.

Simultaneous determination of GFA and its active metabolites in human plasma by liquid chromatography electrospray ionization mass spectrometry and its application to pharmacokinetic studies.

A sensitive and rapid liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method has been developed and validated for simultaneous quantification of guanfu base A (GFA) and its metabolites guanfu base I (GFI) and guanfu alcohol-amine (AA) in human plasma with phenoprolamine hydrochloride (DDPH) as the internal standard. The analytes were extracted from human plasma by using liquid-liquid extraction with ethyl acetate and the LC separation was performed on a Diamonsil C(18) analytical column (150 mm x 2.1 mm i.

Determination of pitavastatin in human plasma via HPLC-ESI-MS/MS and subsequent application to a clinical study in healthy Chinese volunteers.

Background: Pitavastatin is a novel statin used in the treatment of hyperlipemia. We developed and describe a simple and rapid high performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) assay for the determination of pitavastatin in human plasma.

Methods: A Finnigan TSQ Quantum Discovery max system equipped with an electrospray ionization source and a Finnigan Surveyortrade mark HPLC system (Thermo Electron, San Jose, CA) was used employing lovastatin as internal standard (IS) for pitavastatin.