OBJECTIVE:To study the pharmacokinetic characteristics of triflusal capsule in healthy volunteers. METHODS:In ran-domized test,36 healthy volunteers were randomly divided into 3 groups. They were given low-dose,medium-dose and high-dose of Triflusal capsule(300 mg,600 mg and 900 mg),qd,for one day,and then pharmacokinetic study of single dose of Triflusal capsule was conducted;Triflusal capsule medium-dose group was continuously given medicine for 13 days,and then pharmacokinetic study of multiple dose of Triflusal capsule was conducted. The plasma concentration of triflusal was determined by LC-MS/MS,and Zorbax SB-C18 column was used with methanol-0.2% formic acid (80:20,V/V) at the flow rate of 0.2 ml/min. ESI was adopted in MRM mode,negative ion detection was carried out,quantitative analysis m/z 247.1→161.1(triflusal),m/z 294.0→250.0(internal standard, diclofenac sodium). Pharmacokinetic parameters were calculated by using WinNonlin 6.2 software,and the difference of them were compared. RESULTS:The linear range of triflusal were 0.05-20 μg/ml. The main pharmacokinetic parameters of triflusal capsules high-dose,medium-dose and low-dose groups were as follows:t1/2 were (0.45 ± 0.20),(0.47 ± 0.10),(0.43 ± 0.20) h;tmax were (0.56±0.20),(0.60±0.20),(0.47±0.40)h;cmax were(3.30±0.98),(10.65±3.26),(13.96±4.88)μg/ml;AUC0-8 h were(3.99±0.93), (13.29±1.72),(19.62±6.78)μg·h/ml;within dose of 300-900 mg,linear relationship was found between cmax,AUC0-8 h and dose(R2=0.954,0.986). When reaching stable state of multiple dose,average blood concentration was(0.71±0.20)μg/ml;main pharmacokinetic parameters were as follows:AUCs(17.10±4.82)μg·h/ml,t1/2(0.49±0.10)h,tmax(0.85±0.62)h,cmax(11.58±3.99)μg/ml,AUC0-8 h (16.99±4.84)μg·h/ml,AUC0-∞(17.08±4.81)μg·h/ml;accumulation factor(1.28±0.40). tmax and t1/2 of single dose were similar to those of multiple dose. CONCLUSIONS:LC-MS/MS can determine the content of triflusal in human plasma rapidly and accurately, and accumulation phenomena exist in healthy Chinese volunteers,which shows linear pharmacokinetic characteristics.

Pregnancy ; Humans ; Female ; Cesarean Section/adverse effects* ; Abdominal Cavity ; Neoplasms

Quality control is one of the key scientific tissues in the modernization of traditional Chinese medicines (TCM). In order to overcome the deficiencies of assessment indexes, including little systematization and quantification, as well as loose association with clinical efficacy and dosage, a new integrated method named controllability pyramid ( CP) is first proposed in this paper. In addition, some study cases are used to explain how this model is constructed. We hope the establishment of CP could promote the clinical-orien- ted integrated innovation research of TCM, and provide control strategy and technology examples for improving the quality of Chinese medicines and clinical efficacy.
China ; Drug Evaluation ; methods ; standards ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; standards ; Humans ; Medicine, Chinese Traditional ; standards ; Quality Control

Good medicinal herbs, good drugs. Good evaluation method and indices are the prerequisite of good medicinal herbs. However, there exist numerous indices for quality evaluation and control in Chinese medicinal materials. However, most of these indices are non-interrelated each other, as well as having little relationship with efficiency and safety. The results of different evaluatior methods may not be consistent, even contradictory. Considering the complex material properties of Chinese medicinal materials, single method and index is difficult to objectively and comprehensively reflect the quality. Therefore, it is essential to explore the integrated evaluation methods. In this paper, oriented by the integrated evaluation strategies for traditional Chinese medicine quality, a new method called integrated quality index (IQI) by the integration of empirical evaluation, chemical evaluation, and biological evaluation was proposed. In addition, a study case of hypertoxic herb Aconitum carmichaelii Debx. was provided to explain this method in detail. The results suggested that in the view of specifications, the average weight of Jiangyou aconite was the greatest, followed by Weishan aconite, Butuo aconite, Hanzhong aconite, and Anxian aconite; from the point of chemical components, Jiangyou aconite had the characteristic with strong efficacy and weak toxicity, next was Hanzhong aconite, Butuo aconite, Weishan aconite, and Anxian aconite; taking toxicity price as the index, Hanzhong aconite and Jiangyou aconite have the lower toxicity, while Butuo aconite, Weishan aconite, and Anxian aconite have the relatively higher one. After the normalization and integration of evaluation results, we calculated the IQI value of Jiangyou aconite, Hanzhong aconite, Butuo aconite, Weishan aconite, and Anxian aconite were 0.842 +/- 0.091, 0.597 +/- 0.047, 0.442 +/- 0.033, 0.454 +/- 0.038, 0.170 +/- 0.021, respectively. The quality of Jiangyou aconite is significantly better than the others (P < 0.05) followed by Hanzhong aconite, which is consistent with the traditional understanding of genuineness. It can be concluded that IQI achieves the integrated control and evaluation for the quality of Chinese medicinal materials, and it is an exploration for building the good medicinal herbs standards. In addition, IQI provides technical supports for the geoherbalism evaluation, selective breeding, the development of precision decoction pieces, high quality and favourable price in market circulation, and rational drug use.
Aconitum ; chemistry ; Drugs, Chinese Herbal ; standards ; Medicine, Chinese Traditional ; standards

OBJECTIVETo introduce the framework of evidence-based practice with a case of castration-resistant prostate cancer (CRPC) as an example.

METHODSA clinical question was formulated according the clinical scenario. A systematic search was conducted for the published literature in the databases of PubMed, EMBASE, Cochrane Library, Clinical Trial Registries, and Web of Knowledge up to Dec 2014. The identified literature was reviewed for quality appraisal before the evidence was applied to clinical practice.

RESULTSThe treatment was effective and the patient achieved disease remission.

CONCLUSIONEvidence-based practice should be integrated with clinical scenario, current evidence, and patients' willingness, and follow a systematic framework.

Aortic Dissection/complications* ; Aortic Rupture/etiology* ; Humans

Coronary Artery Disease/complications* ; Death, Sudden, Cardiac/etiology* ; Humans ; Myocardial Ischemia/diagnosis*

The specification of decoction pieces and quality uniformity are the important factors to influence the efficacy of clinical medicine. Considering the deficiency of diversity, poor quality uniformity and confusion of decoction pieces specifications, we first propose a new idea of precision decoction pieces (PDP) based on clinical demands and fresh-processed technology. In order to explain the idea, a study case of aconite SUP is provided, including the optimized specification design, processing technology, extraction effects, quality uniformity, and toxic and efficacy variation and so on. The results showed that preparing 5 mm PDP by fresh-cutting is rather simple and practicable, with high efficiency and large yield; then, this technology could significantly decrease the ingredients loss and increase the efficacy components; moreover, it was helpful for achieving the quality uniformity and best extraction effects. This work revealed the quality superiority of PDP, and provided a good strategy and example for the standard of decoction pieces specification and modernization of processing technology.
Aconitum ; chemistry ; Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Particle Size ; Plant Extracts ; chemistry ; pharmacology ; Quality Control

In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.
Aconitum ; chemistry ; Alkaloids ; chemistry ; Amino Alcohols ; chemistry ; Animals ; Cardiotonic Agents ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Heart ; drug effects ; In Vitro Techniques ; Plant Extracts ; chemistry ; Rana catesbeiana ; Spectrometry, Mass, Electrospray Ionization

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.