To date, several clinically important drugs have been identified that interact with commonly used herbs. These drugs include (among others) warfarin, midazolam, digoxin, amitriptyline, indinavir, cyclosporine, tacrolimus and irinotecan. Importantly, many of these drugs have very narrow therapeutic indices. Most of them are substrates for cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). Because drug-herb interactions can significantly affect circulating levels of drug and, hence, alter the clinical outcome, the identification of drugs that interact with commonly used herbal medicines has important implications in drug development. In silico, in vitro, animal and human studies are often used to identify drug interactions with herbs. We propose that drug-herb and herb-CYP interaction studies should be incorporated into drug development.
ABSTRACT:Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is commonly used in the treatment of cardiovascular and central nervous system diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1) in the intestinal absorption of glabridin. The systemic bioavailability of glabridin was approximately 7.5% in rats, but increased when combined with verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation, the permeability coefficient of glabridin based on drug disappearance in luminal perfusates (P lumen ) was approximately 7-fold higher than that based on drug appearance in the blood (P blood ). There is an increasing consumption of herbal medicines in recent years in Asian and Western countries. Their incorporation into the medical care system has been encouraged by the World Health Organization despite the lack of evidence for the efficacy of most herbal drugs. Herbal medicines are usually orally administered with longterm regimens. However, the nature of intestinal absorption of the major ingredients of most herbal medicines is unknown, probably because of a lack of sensitive analytical methods, difficulties in the choice of marker components, and difficulties in the establishment and validation of efficient study models. The widely used traditional Chinese medicine, the root of Glycyrrhiza glabra (licorice), is one of the most commonly used herbal medicines in the world because of its exceptional pharmacological properties recognized by traditional Chinese medicine (Zhu, 1998). Licorice has been used as antidotes,We appreciate the financial support provided by the Australian Institute of Chinese Medicine (Grants R-106-00257 and R-106-00282).J.C., X.C., and J.L. contributed equally to this work. Article, publication date, and citation information can be found at http://dmd.aspetjournals.org. doi:10.1124/dmd.106.010801. ABBREVIATIONS:PgP, P-glycoprotein; MDR, multidrug resistance; MRP, multidrug resistance-associated protein; MDCK, Madin-Darby canine kidney; HPLC, high performance liquid chromatography; HBSS, Hanks' balanced salt solution; DMSO, dimethyl sulfoxide; UDPGA, uridine diphosphate glucuronic acid; 711),vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid; LC-MS, liquid chromatography-mass spectrometry; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide; PBS, phosphate-buffered saline; IS, internal standard; TEER, transepithelial electric resistance; AP, apical; BL, basolateral; t 1/2 , elimination half-life; ABC, ATP-binding cassette; AUC, area under the plasma concentration-time curve; C max , maximum plasma concentration; CL, clearance; V d , volume of distribution; F, systemic bioavailability; P lumen , permeability calculated based on the disappearance of the drug from the intestinal lumen; P blood , permeability calculated based on appearance of the drug in the blood; P app , apparent permeability coefficient; K m , Michaelis-Menten
ObjectiveTo assess safety culture at a public maternity hospital in Shanghai, China, using a sequential mixed methods approach. The study was part of a bigger study looking at the application of the mixed methods approach to assess safety culture in health care in different organizations and countries.MethodologyA mixed methods approach was utilized by first distributing the Safety Attitudes Questionnaire measuring six safety culture dimensions and five independent items to all hospital staff (n=1482) working in 18 departments at a single hospital. Afterward, semistructured interviews were conducted using convenience sampling, where 48 hospital staff from nine departments at the same hospital were individually interviewed.ResultsThe survey received a response rate of 96%. The survey findings show significant differences between the hospital departments in almost all safety culture dimensions and independent items. Similarly, the interview findings revealed that there were different, competing priorities between departments perceived to result in a reduced quality of collaboration and bottlenecks in care delivery. Another major finding was that staff who worked more hours per week would perceive working conditions significantly more negatively. Issues related to working conditions were also the most common concerns discussed in the interviews, especially the issue on high workload. High workload was also reflected in the fact that 91.45% of survey respondents reported that they worked 40 hours or longer per week. Finally, interview findings complemented survey findings, thus providing a more complete and accurate picture of safety culture.ConclusionHospital leaders need to prioritize interventions focused on improving the quality of cross-department collaboration and reducing workload. A mixed methods assessment of safety culture provides more meaningful, targeted results, enabling leaders to prioritize and tailor improvement efforts to increase the impact of an intervention.
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