The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.

Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate "MTX".The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH -401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL).Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays.The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants.MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.

Clinical and Laboratory Factors Related to Seizure and Serotonin Toxicity in Tramadol Intoxication: An Egyptian Study.

BACKGROUND AND OBJECTIVES: Tramadol is a centrally acting analgesic with a lower risk of addiction compared to opioids. Tramadol overdose is becoming a health crisis in Egypt and is associated with serious and severe adverse effects. This study aims to identify clinical and laboratory findings associated with tramadol-induced seizure and serotonin toxicity in adult Egyptian patients with tramadol overdose. METHODS: This prospective study included adult patients admitted for tramadol overdose with or without symptoms of seizure or serotonin toxicity. Basic demographic information, clinical symptoms, laboratory measurements, and plasma tramadol concentrations were collected. RESULTS: A total of 71 patients (79% males) were included in the study. Seizure occurred in 38% of the subjects and was prevalent in male patients with metabolic acidosis or high tramadol concentrations. Serotonin toxicity occurred in 41% of the subjects and was prevalent in patients with hyperthermia, high pulse rate, and high tramadol levels. CONCLUSION: Seizure and serotonin toxicity are severe adverse effects of tramadol overdose that occur in high frequency among young Egyptians. High tramadol concentrations in plasma seem to play a key role in prevalence of seizure and serotonin syndrome in tramadol-intoxicated adult Egyptians.

Design and synthesis of 6-arylpyridine-tethered sulfonamides as novel selective inhibitors of carbonic anhydrase IX with promising antitumor features toward the human colorectal cancer.

Hypoxia, a characteristic feature of solid tumors, develops as a result of excessive cell proliferation and rapid tumor growth exceeding the oxygen supply, and can result in angiogenesis activation, increased invasiveness, aggressiveness, and metastasis, leading to improved tumor survival and suppression of anticancer drug therapeutic impact. SLC-0111, a ureido benzenesulfonamide, is a selective human carbonic anhydrase (hCA) IX inhibitor in clinical trials for the treatment of hypoxic malignancies. Herein, we describe the design and synthesis of novel 6-arylpyridines 8a-l and 9a-d as structural analogues of SLC-0111, in the aim of exploring new selective inhibitors for the cancer-associated hCA IX isoform. The para-fluorophenyl tail in SLC-0111 was replaced by the privileged 6-arylpyridine motif. Moreover, both ortho- and meta-sulfonamide regioisomers, as well as an ethylene extended analogous were developed. All 6-arylpyridine-based SLC-0111 analogues were screened in vitro for their inhibitory potential against a panel of hCAs (hCA I, II, IV and IX isoforms) using stopped-flow CO2 hydrase assay. In addition, the anticancer activity was firstly explored against a panel of 57 cancer cell lines at the USA NCI-Developmental Therapeutic Program. Compound 8g emerged as the best anti-proliferative candidate with mean GI% value equals 44. Accordingly, a cell viability assay (MTS) for 8g was applied on colorectal HCT-116 and HT-29 cancer cell lines as well as on the healthy HUVEC cells. Thereafter, Annexin V-FITC apoptosis detection, cell cycle, TUNEL, and qRT-PCR, colony formation, and wound healing assays were applied to gain mechanistic insights and to understand the behavior of colorectal cancer cells upon the treatment of compound 8g. Also, a molecular docking analysis was conducted to provide in silico insights into the reported hCA IX inhibitory activity and selectivity.

Pharmacokinetics of ampicillin during venovenous extracorporeal membrane oxygenation: A case report.

The presence of extracorporeal membrane oxygenation (ECMO) in addition to underlying critical illness can affect the pharmacokinetics and pharmacodynamics of drugs that are often required to treat this patient population. While ampicillin is the preferred agent for the treatment of susceptible Enterococcus faecalis infections, there are no in vivo pharmacokinetic studies regarding ampicillin dosing in patients receiving ECMO. This case report consists of two patients on venovenous ECMO with E. faecalis bloodstream infections in which ampicillin serum concentrations were measured. Pharmacokinetic parameters were calculated using a one compartment open model. Ampicillin trough levels were 5.87 and 39.2 mg/L for patients A and B, respectively. Based on these results, ampicillin concentrations were found to be above the minimum inhibitory concentration (MIC) for 100% of the dosing interval. The findings of this case report demonstrate that therapeutic concentrations of ampicillin can be obtained in patients on ECMO and therapeutic drug monitoring can be utilized to ensure adequate serum concentrations are achieved.

Changes in dietary habits during Covid-19 lockdown in Egypt: the Egyptian COVIDiet study.

PURPOSE: COVID-19 lockdown changed social habits and lifestyle, including dietary habits, of people worldwide. However, limited information is available about these changes in Egypt. This cross-sectional study investigates the effects of COVID-19 lockdown on dietary habits among the Egyptian populations. METHODS: An online questionnaire, based on sociodemographic data and dietary adherence in accordance with the validated PREDIMED MedDiet Adherence Screener (MEDAS), was used all over the Egyptian governorates. The dietary changes were statistically evaluated for significance in relation to age, gender, body mass index (BMI), education level and governorates. RESULTS: A total of 1010 participants (76% aged below 36 years, 77% female, 22% obese, and 62% university-level education) answered the questionnaire. Respondents ≤ 20 years had a significant increase in weight and consumption of carbonated beverages, commercial pastries, fried and fast food. Egyptians > 50 years old had a significant decrease in physical activity. Underweight people (less than 3% of participants) increased their fast food intake with a prominent rise in weight. However, obese people increased cooking frequency and increased eating times with a decrease in physical activity. Male participants reported increased intake of carbonated beverages and fast food, while female participants increased the intake of homemade pastries with a significant decrease in physical activity. Approximately 50% of participants with postgraduate education reported decreased intake of fast food and carbonated beverages as well as decreased body weight. Residents of Cairo showed a significant increase in vegetable intake, and fried food intake with a decrease in seafood consumption. Participants from the Delta region had a significant increase in pastries intake. CONCLUSION: The findings of this study explored the need for increasing awareness about healthy lifestyle in future lockdown periods.

Linezolid-associated serotonin toxicity: a systematic review.

PURPOSE: This systematic review aims to evaluate the existing evidence associating linezolid to serotonin toxicity when used as monotherapy or when co-administered with other serotonergic agents. METHODS: A systematic literature search using PubMed (till March 2023), IDWeek meetings (2003-2023), the European Congress of Clinical Microbiology and Infectious Disease Annual Meetings (2001-2023), and the American College of Clinical Pharmacy (1999-2023) identified studies and abstracts related to linezolid and serotonin toxicity. RESULTS: A total of 84 studies were included. The data collected in retrospective/observational studies compared the incidence of serotonin toxicity with linezolid monotherapy at 0.0050% and linezolid combination therapy at 0.0134%. All cases which discontinued linezolid and serotonergic agent/s at signs and symptoms of toxicity found symptom resolution; 75% of cases reported serotonin toxicity resolution within 24-48 h after discontinuation. CONCLUSION: Linezolid therapy when optimal should not be deferred due to the risk of serotonin syndrome. The data collected reveals a low prevalence of serotonin toxicity in both linezolid monotherapy and linezolid concurrent with other serotonergic agents.

Natural Products; from the Laboratory to Clinical Practice.

It has been such a great honor to serve as the Guest Editor for this Special Issue, "Exploration on Pharmacokinetics and Pharmacodynamics of Natural Molecules: Current Status and Future Perspectives" [...].

Factors impacting job satisfaction among pharmacists in the Arab world: A qualitative study.

Purpose: This study was undertaken to investigate in-depth the factors impacting job satisfaction among pharmacists in the Arab world and the challenges they encounter in their career path. The outcome of this study should help the local policymakers to take corrective actions to improve pharmacist's satisfaction and therefore enhance quality of patient care. Method: This qualitative study collected responses of pharmacists from 12 Arab countries, as part of a large quantitative survey. Participants added comments to an optional open-ended question regarding work satisfaction. The Qualtrics Survey Software was used to collect the responses. The survey was distributed from March to May 2021 through multiple online channels for filling. The responses collected were analysed to develop themes. An inductive constructivist approach was used for the conceptual thematic analysis as the methodological orientation. Results: A total of 110 responses/comments were received from the study participants. The two largest practice settings of the participants were from hospitals (44.5%) and community pharmacies (28.2%). Almost 40% of responses came from pharmacists practising in Qatar (21.8%) and UAE (18.1%). The survey data demonstrated several reasons impacting job satisfaction among pharmacists practising in the Arab countries. Underestimation of the pharmacists' role, low salaries, lack of motivation and excessive workload were reported as major contributors to job dissatisfaction. On the other hand, professional commitment and the culture of the work setting were the major contributors to job satisfaction. Conclusions: The study provides valuable insights into the aspects concerning pharmacists' satisfaction in the Arab world. Policymakers and other stakeholders need to act upon aspects of pharmacists' job satisfaction and dissatisfaction to ensure potentially better working environment and patient outcomes.

LC-MS/MS bioanalytical method for the quantitative analysis of nifedipine, bisoprolol, and captopril in human plasma: Application to pharmacokinetic studies.

In this study, the development and validation of an accurate and highly sensitive LC-MS/MS method were performed for the estimation of nifedipine, bisoprolol and captopril in real human plasma. Liquid-liquid extraction using tert-butyl methyl ether was efficiently applied for extraction of the analytes from plasma samples. The chromatographic separation was carried out using an isocratic elution mode on the X-terra MS C18 column (4.6 × 50 mm, 3.5 µm). The mobile phase consisted of methanol-0.1% formic acid (95:5, v/v) for determination of nifedipine and bisoprolol and acetonitrile-0.1% formic acid (70:30, v/v) for determination of captopril with a flow rate of 0.5 ml/min. Acceptable results regarding the different validation characteristics of the analytes were obtained in accordance with US Food and Drug Administration recommendations for bioanalytical methods. The developed approach was linear over concentration ranges of 0.5-130.0, 50.0-4,500.0 and 0.3-30.0 ng/ml for nifedipine, captopril and bisoprolol, respectively. The method revealed a sufficient lower limit of quantification in the range of 0.3-50.0 ng/ml, as well as high recovery percentages, indicating high bioanalytical applicability. The proposed method was efficiently applied to a pharmacokinetic evaluation of a fixed-dose combination of the analytes in healthy male volunteers.

Catechin Reduces Blood Pressure in Spontaneously Hypertensive Rats through Modulation of Arachidonic Acid Metabolism.

(1) Background: hypertension affects approximately half of the adults in the United States (roughly 116 million). The cytochrome P450 (CYP)-mediated metabolism of arachidonic acid (AA) in the kidney has been found to play a major role in the pathogenesis of hypertension. This study examines the anti-hypertensive effect of the natural polyphenolic compound catechin (CAT) and investigates if it impacts the metabolism of AA in the kidney in comparison to captopril (CAP): a commonly used antihypertensive drug. (2) Methods: spontaneously hypertensive rats (SHR) were randomly divided into five groups. The treatment groups were administered CAT in drinking water at doses of 10 and 50 mg/kg. A positive control group received CAP at a dose of 10 mg/kg in the drinking water, and one group received both CAP and CAT at doses of 10 mg/kg and 50 mg/kg, respectively. Blood pressure was monitored weekly for five weeks. The activity of the two major enzymes involved in AA metabolism in the kidney, namely CYP4A and soluble epoxide hydrolase (sEH), were analyzed. (3) Results: CAP monotherapy was found to reduce blood pressure compared to the control untreated rats but did not demonstrate any effect on AA metabolism. Low- and high-dose CAT resisted the rise in blood pressure observed in the untreated SHR and significantly lowered blood pressure compared to the control group, respectively. Only rats treated with high CAT doses demonstrated significant inhibition of CYP4A and sEH enzyme activities. The coadministration of CAP and a high dose of CAT resulted in more pronounced blood pressure-lowering effects, but no more significant effects on AA metabolism were found compared to a high dose of CAT alone. (4) Conclusion: the modulation of AA metabolism in the kidney contributes, at least partially, to the blood pressure-lowering effect of CAT in SHR rats.

The Modulation of Arachidonic Acid Metabolism and Blood Pressure-Lowering Effect of Honokiol in Spontaneously Hypertensive Rats.

BACKGROUND: Cardiovascular diseases have consistently been the leading cause of death in the United States over the last two decades, with 30% of the adult American population having hypertension. The metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. METHODS: Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered HON intraperitoneally at concentrations of 5, 20, and 50 mg/kg. Blood pressure was monitored at seven-day intervals. After a total of 3 weeks of treatment, the rats were euthanized and the kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). RESULTS: Rats treated with HON did not experience the rise in blood pressure observed in the untreated SHR. High-dose HON significantly reduced blood pressure and inhibited the activity and protein expression of the CYP4A enzyme in the rat kidney. The activity of the sEH enzyme in renal cytosol was significantly inhibited by medium and high doses of HON. CONCLUSION: Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties.

Exploring job satisfaction among pharmacy professionals in the Arab world: a multi-country study.

OBJECTIVES: The study objectives were to (1) describe the characteristics of the pharmacy professionals and (2) explore the association between job satisfaction and factors, such as work control, work stress, workload and organization and professional commitments. METHODS: This study was a cross-sectional design. The survey items were mainly adapted from the US National Pharmacist Workforce Survey. An electronic (Qualtrics) questionnaire was posted on pharmacist social media in several Arab countries. The survey link was posted from 22 March 2021 to 1 May 2021. The multiple linear regression measured the association between 12 independent variables and pharmacist job satisfaction. KEY FINDINGS: A total of 2137 usable surveys were received from pharmacists (54.7% female) working in 18 Arabic countries. The job satisfaction rate varied among countries in the Arab world. The fields with the highest satisfaction average included pharmaceutical marketing, academia and the pharmaceutical industry. At the same time, pharmacists working in community pharmacy and Ministry of Health/administrative positions had the lowest satisfaction rates. Overall, pharmacist satisfaction was average (3.1 out of 5). The pharmacists had the lowest satisfaction averages with income and job expectations. The pharmacists with bachelor's degrees had significantly lower satisfaction than pharmacists with postgraduate degrees. Male pharmacists had significantly higher job satisfaction compared with female pharmacists. Workload and the feelings of organization and professional commitments had significant positive associations with job satisfaction. CONCLUSIONS: The pharmacy profession in Arabic countries faced several challenges that negatively impacted job satisfaction. Improving work environment, professional management, income and organization loyalty is necessary to enhance pharmacist job satisfaction.

Mechanistic Basis for the Role of Phytochemicals in Inflammation-Associated Chronic Diseases.

Chronic inflammatory diseases occur in a large portion of the population and are associated with a poor diet. Key natural products found in fruits and vegetables may assist in lowering inflammation associated with chronic diseases such as obesity, diabetes, cardiovascular diseases, and cancer. This review seeks to examine the roles of several natural products, resveratrol (RES), quercetin (QUE), curcumin (CUR), piperine (PIP), epigallocatechin gallate (EGCG), and gingerol (GIN), in their ability to attenuate inflammatory markers in specific diseases states. Additionally, we will discuss findings in past and ongoing clinical trials, detail possible phytochemical-drug interactions, and provide a brief resource for researchers and healthcare professionals on natural product and supplement regulation as well as names of databases with information on efficacy, indications, and natural product-drug interactions. As diet and over-the-counter supplement use are modifiable factors and patients are interested in using complementary and alternative therapies, understanding the mechanisms by which natural products have demonstrated efficacy and the types of drugs they interact with and knowing where to find information on herbs and supplements is important for practicing healthcare providers and researchers interested in this field.

Natural Products That Target the Arginase in Leishmania Parasites Hold Therapeutic Promise.

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans worldwide. Because a vaccine is not available and the currently small number of existing drugs are less than ideal due to lack of specificity and emerging drug resistance, the need for new therapeutic strategies is urgent. Natural products and their derivatives are being used and explored as therapeutics and interest in developing such products as antileishmanials is high. The enzyme arginase, the first enzyme of the polyamine biosynthetic pathway in Leishmania, has emerged as a potential therapeutic target. The flavonols quercetin and fisetin, green tea flavanols such as catechin (C), epicatechin (EC), epicatechin gallate (ECG), and epigallocatechin-3-gallate (EGCG), and cinnamic acid derivates such as caffeic acid inhibit the leishmanial enzyme and modulate the host's immune response toward parasite defense while showing little toxicity to the host. Quercetin, EGCG, gallic acid, caffeic acid, and rosmarinic acid have proven to be effective against Leishmania in rodent infectivity studies. Here, we review research on these natural products with a focus on their promise for the development of treatment strategies as well as unique structural and pharmacokinetic/pharmacodynamic features of the most promising agents.

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.

The Impact of Fasting on Major Metabolic Pathways of Macronutrients and Pharmacokinetics Steps of Drugs.

In this review, we have investigated how fasting promotes an adaptive cross-talk between different hormones and metabolic pathways to supply and meet the body's daily energy demands. We highlight in biochemical terms and mechanisms how fasting impacts four metabolic pathways-glycogenolysis, gluconeogenesis, amino acid oxidation, and fatty acid ß-oxidation-that are actively engaged in the metabolism of carbohydrates, proteins, and lipids. Fasting results in reduced insulin secretion and increased glucagon and epinephrine release to prevent or stimulate metabolic reaction(s). Fasting stimulates glycogenolysis, amino acid and glucose oxidation, aminotransferase reactions in skeletal muscle, and promotes gluconeogenesis and urea production in the liver. In addition, fasting promotes gene expression of lipid metabolism in skeletal muscle, the synthesis of ketone bodies in the liver, and intracellular hormone-sensitive lipase activity in adipose tissue. Furthermore, the impact of fasting on reducing cellular damage by mitochondrial reactive oxygen species is discussed. Lastly, we briefly describe the impact of fasting on the four steps of pharmacokinetics-the absorption, distribution, metabolism, and excretion of a few select drugs-with an emphasis on the elimination of drugs related to the cytochrome-P450 family of enzymes.

Development and Validation of High-Throughput Bioanalytical Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Quantification of Newly Synthesized Antitumor Carbonic Anhydrase Inhibitors in Human Plasma.

In the present study, a sensitive and fully validated bioanalytical high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitative determination of three newly synthesized carbonic anhydrases inhibitors (CAIs) with potential antitumor activity in human plasma. The analytes and the internal standard (IS) were extracted using 1.5 mL acetonitrile from only 450 µL aliquots of human plasma to achieve the desired protein precipitation. Chromatographic separations were achieved on Phenomenex Kinetex® C18 column (100 × 4.6 mm, 2.6 µm) using a binary gradient elution mode with a run time of less than 6 min. The mobile phase consisted of solvent (A): 0.1% formic acid in 50% methanol and solvent B: 0.1% formic acid in acetonitrile (30:70, v/v), pumped at a flow rate of 0.8 mL/min. Detection was employed using triple quadrupole tandem mass spectrometer (API 3500) equipped with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was selected for quantitation through monitoring the precursor-to-parent ion transition at m/z 291.9 → 173.0, m/z 396.9 → 225.1, m/z 388.9 → 217.0, and m/z 146.9 → 91.0 for AW-9a, WES-1, WES-2, and Coumarin (IS), respectively. Linearity was computed using the weighted least-squares linear regression method (1/x2) over a concentration range of 1-1000, 2.5-800, and 5-500 ng/mL for AW-9a, WES-1, and WES-2; respectively. The bioanalytical LC-MS/MS method was fully validated as per U.S. Food and Drug Administration (FDA) guidelines with all respect to linearity, accuracy, precision, carry-over, selectivity, dilution integrity, and stability. The proposed LC-MS/MS method was applied successfully for the determination of all investigated drugs in spiked human plasma with no significant matrix effect, which is a crucial cornerstone in further therapeutic drug monitoring of newly developed therapeutic agents.

The Antihypertensive Effect of Quercetin in Young Spontaneously Hypertensive Rats; Role of Arachidonic Acid Metabolism.

Hypertension affects almost 50% of the adult American population. Metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the blood pressure-lowering potential of quercetin (QR), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered QR in drinking water at concentrations of 10, 30, and 60 mg/L. Blood pressure was monitored at seven-day intervals. After a total of seven weeks of treatment, rats were killed and kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Medium- and high-dose QR resisted the rise in blood pressure observed in the untreated SHR and significantly inhibited the activity of the CYP4A enzyme in renal cortical microsomes. The activity of the sEH enzyme in renal cortical cytosols was significantly inhibited only by the high QR dose. Our data not only demonstrate the antihypertensive effect of QR, but also provide a novel mechanism for its underlying cardioprotective properties.

Development and validation of a sensitive and specific LC-MS/MS cocktail assay for CYP450 enzymes: Application to study the effect of catechin on rat hepatic CYP activity.

A sensitive and specific liquid chromatography tandem mass spectrometric (LC-MS/MS) method that enables the simultaneous quantification of probe substrates and metabolites of cytochrome P450 (CYP) enzymes was developed and validated. These substrates (metabolites)-coumarin (7-hydroxycoumarin), tolbutamide (4-hydroxytolbutamide), S-mephenytoin (4-hydroxymephenytoin), dextromethorphan (dextrorphan), and testosterone (6ß-hydroxytestosterone)-were utilized as markers for the activities of the major human CYP enzymes CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. Analytes were separated on Kinetex C18 column (2.1 × 50 mm, 5 µm) using a binary gradient mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Metabolites were detected and quantified by MS using multiple reaction monitoring at m/z 163 → 107.2 for 7-hydroxycoumarin, m/z 235 → 150.1 for 4-hydroxymephenytoin, m/z 287 → 171 for 4-hydroxytolbutamide, m/z 258 → 157.1 for dextrorphan, m/z 305 → 269 for 6ß-hydroxytestosterone, and m/z 237 → 194 for the internal standard. The assay exhibited good linearity over a range of 10-500 ng/mL with acceptable accuracy and precision criteria. As a proof of concept, the developed cocktail assay was successfully used to examine the potential impact of catechin on the activity of the major rat liver CYP enzymes.

A Comprehensive Reflective Journal-Writing Framework for Pharmacy Students to Increase Self-Awareness and Develop Actionable Goals.

Objective. To develop and evaluate the effectiveness of a structured model for reflective journal writing (RJW) and a grading rubric as part of a student portfolio designed to help Doctor of Pharmacy (PharmD) students create actionable goals. Methods. A structured, eight-domain format was developed to engage students in prioritization, identification, exploration, recollection, evaluation, and challenging/solidifying their own knowledge, while assembling an action plan for development (abbreviated using the acronym PIE-RECAP). After completing RJW using this model, students self-identified domains established by the Center for the Advancement of Pharmacy Education (CAPE) that corresponded to their entries. A grading rubric was designed and normalized to require minimal training for use. RJW and other elements of student portfolios were implemented simultaneously across three cohorts (N=296). Twenty-one faculty and staff graders each evaluated 10 to 15 student journal entries. Results. Of 771 journal entries, 648 (84%) met expectations, while 123 (16%) needed to be rewritten. Students identified experiences that were meaningful to them and shared in their RJW entry the knowledge and/or information that they did not know prior to the experience. Common themes identified in the students' RJWs included: curricular experiences (12.7%), cocurricular experiences (18.4%), and experiential training (68.6%). Conclusion. The PIE-RECAP method can be used to guide students in RJW and identify CAPE domains in their personal and professional experiences in pharmacy school. The associated grading rubric can be used to evaluate students' RJW entries and assess their growth in curricular, cocurricular and affective domains relative to their progression.