Pharmacokinetics of IMM-H007 after oral administration in Rhesus monkey using HPLC-MS/MS analysis / 药学学报

A simple, sensitive and reliable method was developed for simultaneous quantification of IMM-H007 and its major active metabolites-M1 and MP in the blood of rhesus monkey using HPLC-MS/MS analysis. The analytes and internal standard (IS) WS070119 were separated using a Capcell PAK ADME Column (2.1 mm×100 mm, 3 μm, Shiseido, Japan) with a gradient mobile phase of methanol/water containing 0.1% formic acid. The detection was performed in positive selected reaction monitoring (SRM) mode with electrospray ionization (ESI) source. Satisfactory linearity was obtained while the inter-and intra-assay precision and accuracy differences were no more than 15% with high recovery and good stability for the quantification, indicating the present method was specific, accurate and reliable. The method was successfully applied to the pharmacokinetic study of IMM-H007 in rhesus monkey. After single oral administration of IMM-H007 (70, 210, 630 mg·kg-1), M1 and MP were detected in blood, while the concentration of IMM-H007 was much lower than its metabolites. The active metabolite MP with linear kinetics had a higher exposure than other analytes in vivo. The results provide an useful and reliable model for pharmacological and toxicological studies of IMM-H007 as well as its clinical application.

A study on the experience of rehabilitation promoting factors in stroke patients / 中华护理杂志

Objective To investigate the rehabilitation promoting factors in stroke patients and to provide references for the design and implementation of effective intervention for rehabilitation of stroke patients.Methods In-depth interviews were conducted among eight stroke patients,and interview data were collected and analyzed.Results Five themes were identified through analysis and classification of the interview data:practical rehabilitation goals,effective rehabilitation training behaviors,overcoming abandonment behaviors and negative emotions,suitable support system,and proper self-adjustment.Conclusion The rehabilitation promoting factors for stroke patients are performing effective rehabilitation training towards effective rehabilitation goals.In this process,patients need to rely on appropriate social support and patients' self-adjustment to overcome abandonment behaviors and negative emotions.These factors form a force to promote rehabilitation during the process of rehabilitation.

Measures of reducing obstetric emergencies hysterectomy incidence

To study the obstetric emergency hysterectomy which can reduce the incidence of measures. In maternity of Xinxiang Central Hospital, the total number of deliveries cases has been up to 50,526 in 20 years, of which 48 cases were retrospectively analyzed for the clinical data of Emergency uterine surgery cases. cases underwent obstetric emergency hysterectomy accounted for 0.095% of total deliveries [48/50 526], in which 11 cases of vaginal delivery, 37 cases of cesarean section. The indications for surgery: 27 cases were cased by placental factors accounted for 56.25%; 14 cases of uterine inertia, accounting for 29.17%; uterine rupture in 4 cases, accounting for 8.33%; 3 cases of coagulopathy, accounting for 6.25%. Where the maternal placental factors hysterectomy is the most common [69.70%, 23/33] and the predominant factor is early maternal uterine inertia [60.00%, 9/15]. There are 74.09% [20/27] of patients with placental abnormalities history of previous cesarean section or uterine surgery. The major risk factors leading to obstetric emergency hysterectomy is placental factors. Preventing the occurrence of placental abnormalities planting actively can effectively reduce the rate of obstetric hysterectomy

Advances in the pharmacological study of Morus alba L / 药学学报

Morus alba L. (mulberry) is a well-known deciduous tree, belonging to the genus of Morus of Moraceae famlily. Its leaves, twigs, roots (bark) and fruits are widely used in the traditional Chinese medicine. The active constituents of mulberry contained flavonoids, alkaloids, steroids, coumarins, with the significant hypoglycemic, hypolipidemic, antihypertension, anti-oxidation, anti-inflammatory, anti-bacterial, anti-tumor and immunomodulatory activities. This review summarized the research progress of the major pharmacological activity, pharmacokinetics and drug-drug interaction based on CYPs and transporters of mulberry and its active constituents.

Chemical-pharmacokinetic-pharmacodynamic fingerprints of Schisandra chinensis alcoholic extract / 药学学报

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

Pharmacokinetics of tenofovir in Beagle dogs after oral dosing of tenofovir dipivoxil fumarate using HPLC-MS/MS analysis / 药学学报

A simple, rapid and sensitive method was developed for the quantification of tenofovir in plasma of Beagle dogs using HPLC-MS/MS analysis. The analytes tenofovir and internal standard (IS) adefovir were separated on a Zorbax SB-C18 column (3.5 microm, 100 mm x 2.1 mm, Agilent, USA) with mobile phase of methanol/water containing 0.3% formic acid using a gradient elution mode at a flow rate of 0.2 mL x min(-1). The plasma sample preparation was a simple deproteinization by the addition of 20% trichloroacetic acid followed by centrifugation. The detection was performed in positive selected reaction monitoring (SRM) mode with an electrospray ionization (ESI) source. The reactions monitored were m/z 288.1-176.2 for tenofovir and m/z 274.1-162.2 for adefovir (IS). Linear detection responses were obtained for tenofovir ranging from 10 to 5 000 ng x mL(-1). The intra- and inter-day precisions (RSD%) was no more than 6.3% with high recovery and good stability for the quantification, indicating the present method was specific, fast, accurate and reliable. The method was successfully applied to the pharmacokinetic study of two tenofovir agents. Tenofovir dipivoxil fumarate (BP0018, test agent) and tenofovir disoproxil fumarate (reference agent) were orally administrated to 8 Beagle dogs according to the 2 x 2 crossover design. Comparing with the reference agent, the longer MRT and t1/2 were obtained in the group of BP0018, while no significant difference was observed in AUC(0-t), AUC(0-infinity), C(max) and t(max) between them, suggesting that tenofovir dipivoxil fumarate was bioequivalent to the tenofovir disoproxil fumarate in Beagle dogs.

Effects of Schisandra chinensis (Wuweizi) constituents on the activity of hepatic microsomal CYP450 isozymes in rats detected by using a cocktail probe substrates method / 药学学报

Effects of constituents from Schisandra chinensis (Wuweizi) on six liver microsomal CYP450 isozymes (CYP1A2, CYP2C6, CYP2C11, CYP2D2, CYP2E1 and CYP3A1/2) were studied in rats in vivo and in vitro. The in vitro incubation was conducted using liver microsomes of rats after multiple dosing of alcoholic/water extract from Schisandra chinensis. A HPLC-MS method was applied to determine the metabolites formation of six CYP450s probe substrates (phenacetin-CYP1A2, dextromethorphan-CYP2D2, diclofenac sodium-CYP2C6, mephenytoin-CYP2C11, chlorzoxazone-CYP2E1 and midazolam-CYP3A1/2) in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. Alcoholic extract of Schisandra chinensis (28-120 microg x mL(-1)) showed significant inhibitory effect on six CYP450 isozymes to a certain extent in vitro. Multiple dosing of Schisandra chinensis alcoholic extract (1.5 g x kg(-1), qd x 7d) had significant induction on CYP2E1 and CYP3A1/2, inhibition on CYP2D2 and CYP2C11, and no effect on CYP2C6 and CYP1A2. Water extract of Schisandra chinensis (100-500 microg x mL(-1)) also exhibited inhibition on the activity of CYP450 isozymes in vitro, whereas multiple administrations (1.5 g x kg(-1), qd x 7d) had significant induction of CYP2E1 and inhibition on CYP2D2, no effect on CYP2C6, CYP3A1/2, CYP1A2 or CYP2C11. The results suggested that the constituents from Schisandra chinensis exhibited the inhibition and induction on six rat liver microsomal CYP450 isozymes to a certain extent in vivo and in vitro. The possibility of interaction between Schisandra chinensis and coadministrative drugs will be considered base on the levels and subtype of CYP450 involved in the drug metabolism.

Effects of bicyclol on the activity and expression of CYP450 enzymes of rats after partial hepatectomy / 药学学报

The present study was performed to investigate the effect of bicyclol on hepatic microsomal cytochrome P450 (CYP) activity, as well as gene and protein expressions in rats after partial hepatectomy (PH). Bicyclol (300 mg x kg(-1)) was given to rats subjected to 70% hepatectomy three times before operation. At 6 and 48 h after PH, blood and liver tissue samples were collected for the measurement of serum alanine aminotransferase (ALT), hepatic microsomal malondialdehyde (MDA) and total hepatic CYP content. The activities of four CYP isozymes were detected with liquid chromatography-mass spectrometry (LC-MS) and the gene and protein expressions were determined by RT-PCR and Western blotting assay. As a result, bicyclol pretreatment markedly inhibited the elevation of serum ALT and hepatic microsomal MDA, and prevented the decrease of total hepatic CYP content in PH rats. In addition, bicyclol significantly attenuated the reduction of CYP2C6 activity and mRNA expression, as well as the reduction of CYP2C11 activity in PH rats. Bicyclol can inhibit the decrease of CYP3A1/2 activity, and up-regulate the mRNA and protein expressions of CYP3A1 and CYP2E1. These results showed that bicyclol pretreatment might ameliorate abnormality in CYP450 isoforms during liver regeneration after PH, and this protective effect was likely due to its anti-oxidative property and enzyme induction.