Working environment for historically marginalized faculty, administrators, and librarians in pharmacy education.

INTRODUCTION: Promoting diversity among faculty, administrators, and librarians in schools and colleges of pharmacy (SCOP) would be beneficial for the recruitment and retention of students from diverse backgrounds. Graduating such diverse pharmacists could assist in reducing healthcare disparities. Promoting diversity requires a climate that is inclusive of people from all backgrounds. The goal of this study was to examine the working environment of historically marginalized faculty, administrators, and librarians within pharmacy education. METHODS: An electronic survey was administered to all faculty, administrators, and librarians listed in the American Association of Colleges of Pharmacy roster. RESULTS: Responses from 339 participants were analyzed. Twenty-seven percent of these participants either observed or personally experienced misconduct during the previous five years. When action was taken, it resulted in the cessation of the misconduct only 38% of the time. Respondents most frequently identified the following as ways to make it easier to address misconduct: support from supervisors, support from peers, and education on how to address misconduct. CONCLUSIONS: Exclusionary, intimidating, offensive, and/or hostile communication/behaviors towards historically marginalized faculty, administrators, and librarians do exist in SCOP. The academy should work towards promoting diversity, equity, and inclusion in SCOP through education and provide administrative and peer support for reporting and managing professional misconduct.

Guidance for Qualitative Research Manuscripts in Pharmacy Education.

The goal of this Best Practice Review is to support researchers in successfully preparing and publishing qualitative research in pharmacy education. Standard practice from the literature and journals' guidance from related fields were reviewed, and recommendations and resources applicable to qualitative research in pharmacy education were compiled for researchers planning to conduct and publish qualitative research. This review provides recommendations, not requirements, for publication in the Journal and is intended to be a guide, especially for authors and reviewers relatively new to the field of qualitative research. Additionally, researchers planning to publish their qualitative research are advised to review available best practices and standards, such as the Consolidated Criteria for Reporting Qualitative Research checklist and the Standards for Reporting Qualitative Research. Given the diverse methodology of qualitative research, it is important for authors to provide sufficient details and justifications of selected methods for transparency and to report collected results in a manner that allows reviewers and readers to adequately assess the validity of their study and the applicability of the findings.

The Tokyo 2020 Olympic and Paralympic pharmacy services during the COVID-19 pandemic.

BACKGROUND: During the Tokyo 2020 Games, pharmacists were required to provide appropriate pharmacotherapeutic care to athletes and officials at the polyclinic. Owing to the worldwide COVID-19 pandemic that was prevalent at the Games, it was imperative to strengthen infection control measures in the setting of such a major sporting event and to prevent and minimize the spread of COVID-19. OBJECTIVE: This study reports on the COVID-19 infection control measures and services provided by the pharmacy at the Tokyo 2020 Games. By evaluating pharmacy operations that took place under the COVID-19 protocol, this study provides insights for the organization of future sporting events, specifically their medical facilities. METHODS: Infection control measures in the pharmacy were implemented in accordance with the manual for dealing with COVID-19 infections. The number and content of issued and dispensed prescriptions were obtained from the electronic medical records and pharmacy department systems. These data were compared with those of the London 2012 Games, which were used as a reference for the pharmacy operations at the Tokyo 2020 Games. RESULTS: The participating pharmacists were fully trained in infection control measures. The number of prescriptions issued during the Olympics and Paralympics were 1120 and 1022, respectively. Prescriptions issued at the fever clinic accounted for 4% of the total number (77/2142). No influenza antiviral medications were prescribed, though medications to alleviate cold-like symptoms were issued. Compared to the London 2012 Games, there was a decrease (-59%) in the number of prescriptions. CONCLUSION: The positive impact of COVID-19 infection control measures was evident. The volume of prescriptions at the Tokyo 2020 Games was lower than that at the London 2012 Games. It was inferred that this was due to thorough infection control measures as well as enhanced pre-entry medical checkups before entering Japan, which reduced the incidence of diseases.

Characteristics of Successful International Pharmacy Partnerships.

Recommendations for global pharmacy collaborations are predominately derived from US institutions. This study utilized semi-structured interviews of global collaborators to assess important partnership components. Interviewees stated personal connections and understanding of each other's programs/systems were key components. Additionally, collaborators indicate that mutual benefits between partners can exist without the requirement for bidirectional exchange of learning experiences, and request and value partners and learners who are culturally aware, global citizens. This structured interview approach provided key insight into how to develop mutually beneficial, sustainable partnerships and provides additional confirmation that the five pillars of global engagement align with an international audience.

Baseline Assessment of Systemic Racism Education in Pharmacy Curricula.

Objective. To determine, by survey, the inclusion of systemic racism education in US Doctor of Pharmacy (PharmD) curricula and identify barriers and facilitators to addressing this content.Methods. A survey was developed and distributed to curricular representatives at US colleges and schools of pharmacy. The survey assessed inclusion of systemic racism education in curricula, faculty involvement in teaching systemic racism content, barriers to adding systemic racism content in curricula, and future curricular plans. Data were analyzed using descriptive statistics for institutional background information, curricular content, and barriers to inclusion. Relationships between the inclusion of systemic racism content at public versus private programs were examined, and associations between traditional and accelerated programs were assessed.Results. Fifty-eight colleges and schools of pharmacy provided usable responses. Of the respondents, 84% indicated that teaching systemic racism content and its impact on health and health care was a low priority. For 24% of respondents, systemic racism content was not currently included in their curriculum, while 34% indicated that systemic racism content was included in one or more courses or modules but was not a focus. Despite systemic racism content being offered in any didactic year, it was rarely included in experiential curricula. Top barriers to inclusion were lack of faculty knowledge and comfort with content and limited curricular space. No significant differences were found between program types.Conclusion. Based on the current level of systemic racism education and barriers to inclusion, faculty need training and resources to teach systemic racism concepts within pharmacy curricula. The inclusion of systemic racism concepts and guidance in the Accreditation Council for Pharmacy Education's Accreditation Standards could help to drive meaningful change and promote health equity.

Impact of an educational flyer and sensitization on performance-enhancement attitudes of bodybuilders in United Arab Emirates.

Background: A high proportion of bodybuilders use supplements to improve performance, with some turning to prohibited substances and methods. The attitudes of bodybuilders towards performance enhancement may be gauged through surveys such as the Performance Enhancement Attitude Scales (PEAS). Educational interventions are recommended as part of anti-doping measures. The objective of this project was to assess the impact of a pharmacy-led intervention using an antidoping educational flyer and the performance enhancement attitude scale to measure the attitude of bodybuilders in the United Arab Emirates (UAE). Methods: The PEAS eight-item short form questionnaire was administered to male bodybuilders in the UAE. The PEAS was conducted before and after administration of an educational flyer concerning the problems associated with supplement use among bodybuilders. The Wilcoxon Signed-Rank and Kruskal Wallis tests were used for data analysis. Results: A total of 218 bodybuilders, who reported taking dietary supplements, filled out the survey both pre and post viewing the antidoping educational flyer. A difference was observed between the full-time professional bodybuilders, students, and part-time bodybuilders with other primary occupations (p-value <0.05). In addition, PEAS score decreased among the study population for all eight PEAS items (p-value <0.05). Conclusions: The pharmacy-led intervention using an antidoping educational flyer and sensitization by PEAS achieved more favorable scores, suggesting a significant shift of opinion toward avoiding use of performance enhancing substances among the bodybuilder study population. More research is required on sustaining the attitude and demonstrating the impact on doping behavior.

Reconsidering Sports Pharmacists and Anti-Doping Education as the World Celebrates the Olympic and Paralympic Games.

The Tokyo Olympic and Paralympic Games in 2021 presented an opportunity for pharmacists to recognize the uniqueness of sports pharmacy as a developing field and to understand the importance of anti-doping education among patient-athletes. Patient-athletes make up a distinct patient population, and pharmacists are well positioned to support athletes' therapeutic decisions. Pharmacists need to be able to search for and interpret drug information to take care of this special population appropriately. The purpose of this commentary is to facilitate a discussion on what changes or reinforcement might help train pharmacists to become equipped with adequate knowledge and skills to support safe use of drugs among patient-athletes. While effective resources and tools have become more widely available, pharmacists' awareness of and training in the field of sports pharmacy continue to be needed. No matter where they practice, pharmacists should be ready to promote "the spirit of sport" and defend the importance of "clean" sport for their patient-athletes.

Pharmacokinetic Considerations in Amputees.

PURPOSE: The purpose of this article is to review the currently available assessment tools for measuring renal function, body weight, and body surface area in the amputee population. METHODS: PubMed and Web of Science were searched using the following key terms: amputation, dose adjustment, and estimation of body weight. Articles published in languages other than English were excluded from the search. RESULTS: Despite the increasing prevalence of amputations, there is little literature available that discusses its impact on the patient and how these physiological changes can affect pharmacokinetics. Very little information is available to guide dose adjustment in this patient population. This article discusses several factors to consider when determining optimum dosing regimens in patients with different levels of amputations. CONCLUSION: This article will evaluate the applicability of methods mentioned in existing literature for measuring changes in renal function, body weight, and body surface area in amputees.

COVID-19 Pandemic Challenges and Lessons Learned by Pharmacy Educators Around the Globe.

The coronavirus identified in 2019 (COVID-19) has affected peoples' lives worldwide. This pandemic forced both pharmacy faculty members and students to adapt to a new teaching and learning environment not only in the United States but around the globe. Pharmacy educators faced challenges and opportunities to convert classroom learning and experiences, as well as student assessments, to a remote or online format. The unique approaches taken to overcome difficulties in various countries showed pharmacy faculty members' resilience in the face of adversity and their determination to continue providing education to students. The pandemic also shed light on areas needing improvement for pharmacy educators to work on in the future.

Cultural Sensitivity and Global Pharmacy Engagement in Asia: India, Indonesia, Malaysia, Philippines, and Vietnam.

Schools and colleges of pharmacy in the United States increasingly interact with those in Asian countries for various purposes such as education and research. For both those visiting and those hosting, it is important to understand and respect the culture of the other's country to enrich these interactions. This paper, the second of two manuscripts on Asian countries, focuses on India, Indonesia, Malaysia, Philippines, and Vietnam. For each country, the following information is provided: general introduction, health care system, pharmacy practice, and pharmacy education, stereotypes and misconceptions, recommendations for US-based health care professionals, faculty members, and students who visit these Asian countries, and recommendations for them to host visitors from these Asian countries. The aim of this paper is to assist US health care professionals, faculty members, and students in initiating and promoting a culturally sensitive engagement.

Cultural Sensitivity and Global Pharmacy Engagement in the United States.

Objective. To provide a resource for schools and colleges of pharmacy in different regions of the world that are considering sending their students and faculty members to the United States for training. Methods. A literature review (2000-2018) was conducted that involved database and Internet searches using specific keywords and terms. Information was also solicited from authors in different regions of the United States who have hosted international students and faculty members. Recommendations for pharmacists and other health care practitioners on culturally sensitive engagement were formulated. Results. Global engagement between schools and colleges of pharmacy from different regions of the world and the United States is increasing. In addition to various cultural aspects, general information about the US health care system, pharmacy education programs, and pharmacy practice were found to be available to individuals who are charged with organizing and facilitating these exchanges. Common stereotypes and misconceptions about the United States were also identified. Conclusion. For international learners to have an enriching and fruitful engagement while in the United States, an understanding of American culture in general as well as the unique cultural aspects of different regions of the country as provided in this paper is critical.

Cultural Sensitivity and Global Pharmacy Engagement in Asia: China, Japan, South Korea, and Taiwan.

Interest in global engagement among schools and colleges of pharmacy in the United States and Asian countries is growing. To develop fruitful relationships and engage in mutually enriching experiences, the cultural aspects of these countries need to be understood and respected. The aim of this paper is to facilitate culturally sensitive interactions between practitioners, faculty members, and students in the United States and those in Asian countries when they engage in health care practice and/or education. This paper introduces general information about China (including Macau and Hong Kong), Japan, South Korea, and Taiwan. Unique characteristics of the health care system and pharmacy education are described for each country. Stereotypes and misconceptions are discussed. Recommendations are included for initiating interactions and developing learning programs and scholarly collaborations while promoting culturally sensitive engagement. These recommendations are provided for US scholars, health care professionals, and students traveling to these countries as well as for those hosting visitors from these countries in the United States.

Report of the 2018-2019 Research and Graduate Affairs Committee.

The 2018-2019 Research and Graduate Affairs Committee (RGAC) was charged with critically evaluating the leadership development support necessary for pharmacy researchers, including postdoctoral trainees, to develop the skills needed to build and sustain successful research programs and analyzing how well those needs are being met by existing programs both within AACP and at other organizations. The RGAC identified a set of skills that could reasonably be expected to provide the necessary foundation to successfully lead a research team and mapped these skills to the six domains of graduate education in the pharmaceutical sciences established by the 2016-2017 RGAC (Table 1). In addition, the RGAC identified competency in team science and the bench-to-bedside-to-beyond translational spectrum as being critical elements of research leadership. The universality of these skills and their value prompted the RGAC to make two related recommendations to AACP: [Table: see text] Recommendation 1: AACP should promote the development and use of strategies to ensure intentional and ongoing professional development, such as Individual Development Plans. Recommendation 2: AACP should explore collaborative research leadership development opportunities between faculty at research-intensive institutions and faculty at non-research-intensive institutions. The RGAC also examined programs available at AACP and other national organizations that could help pharmacy faculty develop foundational skills for research leadership (Table 2). The RGAC administered two surveys, one to administrators responsible for research at colleges and schools of pharmacy and one to faculty members at pharmacy schools, to gather information about training needs, programming and support available for research leadership development. Administrators and faculty agreed that research is important for career advancement for faculty, and almost all administrators reported their schools provide funds, release time and mentoring for participation in research career development. However, a lack of faculty awareness regarding programs and available support may be a barrier to participation. The RGAC therefore makes two recommendations and one suggestion related to AACP programming: [Table: see text] Recommendation 3: AACP should expand research leadership development opportunities building from existing programs such as ALFP and AACP Catalyst, with consideration placed on developing programs that promote collaborative research. Recommendation 4: AACP should collaborate with other professional organizations to expand research leadership development opportunities across the academy. Suggestion 1: Colleges and schools of pharmacy should take a proactive role in promoting and facilitating research leadership development for faculty. The RGAC separately examined the research leadership development needs of postdoctoral trainees, recognizing the distinct needs of trainees along the PhD or PhD/PharmD, PharmD/fellowship, and PharmD/residency paths. A review of organizational resources and opportunities for post-doctoral trainees available from national organizations, including AACP, was undertaken (Table 5). The RGAC sees an opportunity for AACP to foster research development of those trainees whose career track will likely be in clinical practice and makes one recommendation and one suggestion related to postdoctoral trainees: Recommendation 5: AACP should support and/or develop programs and activities for pharmacy residents seeking to transition into faculty positions to acquire the skills necessary to develop and lead research programs. Suggestion 2: Colleges and schools of pharmacy should include postdoctoral trainees with academic interests in research leadership development opportunities available to junior faculty. In addition, the RGAC proposed one policy statement that was adopted July 2019 by the AACP House of Delegates: Policy Statement: AACP recognizes the positive role that research leadership development can play in the success of early and mid-career faculty.

Integration of mentored self-directed learning (MSDL) through both group and individual presentations in an accelerated modified block program.

BACKGROUND AND PURPOSE: Project aim was to examine the feasibility and logistics of mentored self-directed learning (MSDL) through group and individual presentations in an accelerated modified block curriculum. Perspectives of students and faculty members toward the incorporation of MSDL were also explored. EDUCATIONAL ACTIVITY AND SETTING: During a two-week pharmacotherapy block, students made group presentations requiring two elements: a case presentation on curricular content (Element-1) and an inclusion of "novel" information students did not receive didactically (Element-2). Curricular content for Element-1 stemmed from a pharmacotherapy course on gastroenterology and nutrition, and individual presentations were scheduled during a semester-long skill-based course. Surveys on student perspectives were conducted at baseline, after group presentations, and after individual presentations. Faculty members also provided feedback and evaluations. FINDINGS: Whereas 58% of students considered a case presentation (Element-1) more valuable for their learning than inclusion of Element-2, 78% of faculty's responses indicated the incorporation of both Elements was valuable. For the following individual presentations, 73% of students were willing and able to present a topic not extensively addressed in the didactic curriculum by employing MSDL. Students improved their confidence in preparing and making presentations for peers and faculty/preceptors through the MSDL activities (p < 0.025). At the end of this project, the faculty determined 88% of students were ready to give a presentation considered appropriate for Advanced Pharmacy Practice Experience. DISCUSSION: MSDL through group and individual presentation activities were feasible and provided a valuable learning experience for students in an accelerated modified block curriculum.

A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis.

Pioglitazone is used effectively to treat non-alcoholic steatohepatitis (NASH), but there is marked variability in response. This study examined whether genetic variation contributes to pioglitazone response variability in patients with NASH. This genetic substudy includes 55 participants of a randomized controlled trial designed to determine the efficacy of long-term pioglitazone treatment in patients with NASH. The primary outcome of the clinical trial was defined as ≥2-point reduction in the non-alcoholic fatty liver disease activity score (NAS). In this substudy, single nucleotide polymorphisms (SNPs) in putative candidate genes were tested for association with primary and secondary outcomes. A genetic response score was constructed based on the sum of response alleles for selected genes. The genetic response score was significantly associated with achievement of the primary outcome (odds ratio 1.74; 95% CI 1.27-2.54; p = 0.0015). ADORA1 rs903361 associated with resolution of NASH (p = 0.0005) and change in the ballooning score among Caucasian and Hispanic patients (p = 0.0005). LPL rs10099160 was significantly associated with change in ALT (p = 0.0005). The CYP2C8∗3 allele, which confers faster pioglitazone clearance in allele carriers, was associated with change in fibrosis score (p = 0.026). This study identified key genetic factors that explain some of the inter-individual variability in response to pioglitazone among patients with NASH.

Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients From the PEAR Study (Pharmacogenomic Evaluation of Antihypertensive Responses).

BACKGROUND: Plasma renin is an important regulator of blood pressure (BP). Plasma renin activity (PRA) has been shown to correlate with variability in BP response to antihypertensive agents. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive Responses). METHODS: Multiple linear regression analysis was performed in 461 whites and 297 blacks using an additive model, adjusting for age, sex, and ancestry-specific principal components. Top SNPs were prioritized by testing the expected direction of association for BP response to atenolol and hydrochlorothiazide. Top regions from the BP response prioritization were tested for functional evidence through differences in gene expression by genotype using RNA sequencing data. Regions with functional evidence were assessed for replication with baseline PRA in an independent study (PEAR-2). RESULTS: Our top SNP rs3784921 was in the SNN-TXNDC11 gene region. The G allele of rs3784921 was associated with higher baseline PRA (ß=0.47; P=2.09×10-6) and smaller systolic BP reduction in response to hydrochlorothiazide (ß=2.97; 1-sided P=0.006). In addition, TXNDC11 expression differed by rs3784921 genotype (P=0.007), and rs1802409, a proxy SNP for rs3784921 (r2=0.98-1.00), replicated in PEAR-2 (ß=0.15; 1-sided P=0.038). Additional SNPs associated with baseline PRA that passed BP response prioritization were in/near the genes CHD9, XIRP2, and GHR. CONCLUSIONS: We identified multiple regions associated with baseline PRA that were prioritized through BP response signals to 2 mechanistically different antihypertensive drugs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00246519.

Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia.

Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. Many studies have explored the variation in statins' pharmacokinetic and pharmacodynamic parameters; however, to our knowledge, few have established definitive relationships between the genetic polymorphisms and patient outcomes, such as cardiovascular events. In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy.

Effect of Low-Furanocoumarin Hybrid Grapefruit Juice Consumption on Midazolam Pharmacokinetics.

The objectives of this study were to investigate the effect of grapefruit juice low in furanocoumarins on CYP3A activity and to summarize previous findings of enzyme inhibition measured by the metabolism of midazolam after intake of grapefruit juice. Twelve healthy volunteers participated in a prospective, randomized, double-blinded, 3-way crossover clinical study to determine the effect of regular grapefruit juice (RGJ) and a novel, low-furanocoumarin hybrid grapefruit juice (HGJ) on the metabolism of oral midazolam, used as a probe for in vivo CYP3A activity, compared with water as a control. The RGJ was 100% hand-squeezed "Hudson" grapefruit juice, and the HGJ contained low amounts of furanocoumarin constituents. The point estimates (90% confidence intervals) for the RGJ/water midazolam AUC geometric mean ratio was 122% (107-140). The point estimate for the HGJ/water midazolam AUC ratio was within the 80% to 125% bioequivalence range, indicating an absence of interaction. This finding also prompted a systematic review of available evidence on the pharmacokinetic alteration of midazolam by grapefruit juice. Although most studies demonstrated alteration in midazolam pharmacokinetics supporting inhibition of CYP3A activity as a likely mechanism, the cohorts included in these studies and the extent of the pharmacokinetic interaction varied widely. The current study indicated grapefruit juice-drug interaction varies substantially based on patient characteristics and/or grapefruit juice product-related factors, including the amount of furanocoumarin constituents present in the juice.

A validated liquid chromatography tandem mass spectrometry method for simultaneous determination of pioglitazone, hydroxypioglitazone, and ketopioglitazone in human plasma and its application to a clinical study.

A simple and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of pioglitazone and its active metabolites hydroxypioglitazone and ketopioglitazone in human plasma. Samples were processed by protein precipitation with acetonitrile and selective phospholipid depletion in a 96-well plate format. The method used deuterated internal standards for each analyte. Chromatographic separation was achieved with gradient elution on a Hypersil GOLD C18 column. The mass spectrometer was operated in electrospray positive ion mode with detection by selected reaction monitoring using the transitions m/z 357.1>134.0 for pioglitazone, m/z 373.1>150.0 for hydroxypioglitazone, and m/z 371.0>148.0 for ketopioglitazone. A linear standard curve was established for the range of 10-1800ng/mL for all three analytes. Intra-run and inter-run precision and accuracy (relative error) were less than 15%, and the mean extraction recoveries of all analytes were more than 87.8%. The validated method is sensitive and selective and was successfully applied to analyze clinical samples obtained from patients with nonalcoholic fatty liver disease taking pioglitazone.

The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity.

Milk thistle (Silybum marianum) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders. The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts. In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 (P450) enzymes. However, determining the potential for clinically significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results. The aim of the present study was to determine the effect of a standardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period. CYP1A2, CYP2C9, CYP2D6, and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs, caffeine, tolbutamide, dextromethorphan, and midazolam, to nine healthy volunteers before and after exposure to a standardized milk thistle extract given thrice daily for 14 days. The three most abundant falvonolignans found in plasma, following exposure to milk thistle extracts, were silybin A, silybin B, and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators. The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration. Exposure to milk thistle extract produced no significant influence on CYP1A2, CYP2C9, CYP2D6, or CYP3A4/5 activities.