An analysis of the intention of female pharmacy students to work in community pharmacy settings in Saudi Arabia using the theory of planned behavior.

Objective: This study aimed to determine the intention of female Saudi pharmacy students to work in community pharmacies and the factors associated with this intention. Methods: This cross-sectional study was conducted between April 2022 and June 2022 and included female students from pharmacy colleges in Saudi Arabia. The survey was created based on the Theory of Planned Behavior. It included items that measure student intentions, attitudes, subjective norms, and perceived behavioral control regarding working in community pharmacies in Saudi Arabia. The study also included items that assessed sociodemographic characteristics, pharmacy program degrees, training, and job preferences of students. Results: A total of 407 participants completed the survey. The average age was 21.8 (±1.6) years, and most participants were Saudi nationals (97.79 %). The intention of participants to work in community pharmacies after graduation was low (mean = 3.2 ± 1.8; range: 1-7). Slightly positive attitudes toward working in a community pharmacy after graduation were revealed as participants showed an overall attitude mean of 4.5 ± 1.6 (range: 1-7). Furthermore, the participants perceived a low social pressure toward working in a community pharmacy after graduation (mean of 3.3 ± 1.9; range: 1-7). The intention of female pharmacy students to work in community pharmacies was significantly predicted by attitudes (p-value < 0.0001), perceived behavioral control (p-value = 0.0017), nationality (p-value = 0.0151), residence in the Saudi Arabian region (p-value = 0.0013), monthly income (p-value = 0.0231), pharmacy degree program (p-value = 0.0035), training received in community pharmacies (p-value = 0.0145), had a relative working in a community pharmacy (p-value = 0.0257), and preference to work in community pharmacies after graduation (p-value = 0.0001). Conclusion: Female pharmacy students in Saudi Arabia had a low intention to work in community pharmacies, a positive attitude toward working in community pharmacies, and perceived no social pressure to work in them. A positive attitude and behavioral perception of control toward working in community pharmacies were demonstrated among pharmacy students who study at a university outside Riyadh, undertaking a bachelor's degree in pharmacy, have a monthly income higher than 5000 Saudi riyals (USD 1,333.3), previously received training in community pharmacies, having a relative working in a community pharmacy, prefer to work in community pharmacies after graduation.

The influence of telemedicine in primary healthcare on diabetes mellitus control and treatment adherence in Riyadh region.

Several studies have found that telemedicine has the potential to enhance the outcomes of patients with diabetes. This study aimed to determine the impact of telemedicine on the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) in Saudi Arabia. We conducted a cross-sectional study among T2DM patients in selected primary healthcare centers in Riyadh, Saudi Arabia, from March 1, 2023, to August 20, 2023. We looked at how telemedicine affected HbA1c control, adherence, the number of diabetic complications, and polypharmacy using adjusted multivariable logistic regression models. Among the 583 patients, 140 (24.05 %) received care via telemedicine, while 442 (75.95 %) received in-person care. Patients who utilized telemedicine had significantly better glycemic control than those who received in-person care only (AOR = 5.123, 95 % CI = 3.107-8.447). Telemedicine also showed positive effects on treatment adherence (AOR = 2.552, 95 % CI = 1.6284-4.2414). Telemedicine can effectively reduce diabetic complications (AOR = 0.277, 95 % CI = 0.134-0.571). Regarding polypharmacy, patients with telemedicine use were less likely to report polypharmacy (AOR = 0.559, 95 % CI = 0.361-0.866). Telemedicine is considered one of the factors that improve HbA1c management and might increase therapeutic adherence and reduce diabetic complications and polypharmacy.

Beliefs, awareness, use, and factors associated with herbal supplements usage among patients with chronic diseases-A cross-sectional insight from Alkharj, Saudi Arabia.

BACKGROUND: Herbal supplements (HSs) are used to treat a variety of diseases and ailments. Individuals with chronic diseases are at a higher risk of having adverse events and drug interactions from the use of HSs. AIM: This study determined the beliefs, awareness, use, and factors associated with HSs usage among patients with chronic diseases in Alkharj, Saudi Arabia. METHOD: A cross-sectional study was conducted among patients with chronic diseases between February and June 2019. Face-to-face interviews were conducted at various out-patient clinics in different hospitals. Patients diagnosed with chronic diseases were included in the study. Data were analyzed by descriptive, comparative, and inferential statistics using SAS ver. 9.4. RESULTS: The study participants were consisted of 533 patients, with mean age 53.6 ±12.9 years. The most prevalent chronic diseases were diabetes mellitus (67.7%), followed by hypertension (54.8%), and hyperlipidemia (53.8%). Among the studied participants, 336 (63%) had used at least one HS, whereby the most commonly used HSs were ginger (74.7%), mint (72%), and cumin (66.7%). Almost 78% of HSs users did not consult any healthcare provider about their use. HSs use varied significantly between female and male participants (p<0.05), whereby 61.5% of female participants used HSs in comparison to the male participants (38.5%). Gender (AOR 0.328; 95% CI 0.139-0.772; p = 0.0107), number of chronic diseases (AOR 1.585; 95% CI 1.084-2.318; p = 0.0312), and hyperlipidemia (AOR 2.818; 95% CI 1.507-5.269; p = 0.0.0012) were the pure factors of HSs use among the studied patients. CONCLUSION: The results of this study showed that HSs usage was high among patients with chronic diseases in Saudi Arabia. Concurrent usage of HSs with drugs should be well-discussed with healthcare providers to avoid potential adverse events or drug interactions especially among patients with chronic diseases.

Therapeutic Drug Monitoring of Voriconazole in Critically Ill Pediatric Patients: A Single-Center Retrospective Study.

BACKGROUND AND OBJECTIVE: Voriconazole pharmacokinetics are highly variable in pediatric patients, and the optimal dosage has yet to be determined. The purpose of this study was to describe voriconazole pharmacokinetic and pharmacodynamic targets achieved and evaluate the efficacy and safety of voriconazole for critically ill pediatrics. METHODS: This is a single-center retrospective study conducted at a pediatric intensive care unit at a tertiary/quaternary hospital. Pediatrics admitted to the pediatric intensive care unit and who received voriconazole for a proven or suspected fungal infection with at least one measured trough concentration were included. The primary outcomes included the percentage of pediatric patients who achieved the pharmacokinetic and pharmacodynamic targets. Secondary outcomes included assessing the correlation between voriconazole trough concentrations and clinical/microbiological outcomes. All statistical analyses were performed using the R statistical software and Microsoft Excel. Multiple logistic regression was used to assess the predictors of both clinical and microbiologic cures. Multiple linear regression was used to determine significant factors associated with trough concentrations. RESULTS: A total of 129 voriconazole trough concentrations were measured from 71 participants at steady state after at least three doses of voriconazole. The mean (± standard deviation) of the first and second trough concentrations were 2.9 (4.2) and 2.3 (3.3) mg/L, respectively. Among the first trough concentrations, only 33.8% were within the therapeutic range (1-5 mg/L), 46.5% were below the therapeutic range, and 19.7% were above the therapeutic range. A clinical cure occurred in 78% of patients, while a microbiologic cure occurred in 80% of patients. CONCLUSIONS: Voriconazole trough concentrations vary widely in critically ill pediatric patients and only a third of the patients achieved therapeutic concentrations with initial doses.

Access and Disparities in the Use of Telemedicine Among Patients with Chronic Conditions in Saudi Arabia: A Cross-Sectional Study.

Purpose: This study investigated the access to and disparities in telemedicine use among patients with chronic conditions in Riyadh, Saudi Arabia. Patients and Methods: A cross-sectional study of randomly selected primary healthcare centers was conducted to ensure that each of the 17 municipalities in Riyadh were represented. Three hundred and forty-two participants who completed the questionnaire were interviewed using a standardized questionnaire. The relationship between demographic and socioeconomic factors and telemedicine utilization was evaluated using the chi-square test and multivariable mixed-effects logistic regression model. Results: Among the 342 participants, the study revealed that 25.73% of the patients utilized telemedicine. Older participants had lower odds of telemedicine use than did those aged ≤ 30 years [adjusted odds ratio (AOR) = 0.112, 95% confidence interval (CI) = 0.045-0.279 for 50-59 years; AOR = 0.19, 95% CI = 0.076-0.474 for 60-69 years; AOR = 0.223, 95% CI = 0.092-0.542 for ≥ 70 years]. Female sex (AOR = 2.519, 95% CI = 1.44-4.408), having a higher education level (AOR = 3.434, 95% CI = 1.037-7.041 for secondary education and AOR = 5.87, 95% CI = 2.761-8.235 for higher education), and living in urban areas (AOR = 2.721, 95% CI = 1.184-6.256) were associated with higher odds of telemedicine use. Among socioeconomic factors, employed participants had higher odds of telemedicine use (AOR = 4.336, 95% CI = 2.3-8.174). Furthermore, compared to those with the highest socioeconomic status (SES) index, those with the lowest SES were less likely to use telemedicine than those with the highest SES index (AOR = 0.193, 95% CI = 0.055-0.683 for the lower bottom (poorest). Conclusion: This study highlights a significant disparity in the utilization of telemedicine services across different populations, primarily due to demographic and socioeconomic factors.

Knowledge, perceptions, and readiness of telepharmacy among community pharmacists.

Telepharmacy is a practical part of telemedicine that refers to providing pharmaceutical services within the scope of the pharmacist's obligations while maintaining a temporal and spatial distance between patients, users of health services, and healthcare professionals. The present study was a cross-sectional study conducted among community pharmacists in Saudi Arabia between March and May 2022 to assess their knowledge, perceptions, and readiness for telepharmacy. The survey was filled out by 404 respondents. The majority of respondents were male (59.90%) and the age of more than half of them was between 30 and 39 years old (54.46%). Most participants worked in urban areas (83.66%), and 42.57% had less than five years of experience in a pharmacy. Most participants agreed that telepharmacy is available in Saudi Arabia (82.67%). Approximately 70% of pharmacists felt that telepharmacy promotes patient medication adherence, and 77.72% agreed that telepharmacy increases patient access to pharmaceuticals in rural areas. More than 72% of pharmacists said they would work on telepharmacy initiatives in rural areas for free, and 74.26% said they would work outside of usual working hours if necessary. In the future, this research could aid in adopting full-fledged telepharmacy pharmaceutical care services in Saudi Arabia. It could also help academic initiatives by allowing telepharmacy practice models to be included as a topic course in the curriculum to prepare future pharmacists to deliver telepharmacy services.

Interethnic differences in drug response: projected impact of genetic variations in the Saudi population.

Ethnicity is known to have an impact on drug responses. This is particularly important for drugs that have a narrow therapeutic window, nonlinearity in pharmacokinetics and are metabolized by enzymes that demonstrate genetic polymorphisms. However, most clinical trials are conducted among Caucasians, which might limit the usefulness of the findings of such studies for other ethnicities. The representation of participants from Saudi Arabia in global clinical trials is low. Therefore, there is a paucity of evidence to assess the impact of ethnic variability in the Saudi population on drug response. In this article, the authors assess the projected impact of genetic polymorphisms in drug-metabolizing enzymes and drug targets on drug response in the Saudi population.

Knowledge, Perceptions, and Readiness of Telepharmacy among Hospital Pharmacists in Saudi Arabia.

Telepharmacy is a technology-based service that provides promoted services such as counseling, medication administration and compounding, drug therapy monitoring, and prescription review. It is unclear whether hospital pharmacists possess the necessary knowledge, attitudes, and willingness to practice telepharmacy. The current study sought to investigate Saudi Arabian hospital pharmacists' understanding, attitudes, and level of preparedness for telepharmacy services. A total of 411 pharmacists responded to the survey. Only 43.33% of the respondents agreed that telepharmacy is available in Saudi Arabia and 36.67% of the respondents agreed that patients in rural areas can have more medication access and information via telepharmacy. Only 29.33% of pharmacists agreed that telepharmacy improves patient medication adherence, and about 34.00% of the pharmacists agreed that telepharmacy saves patients money and time by eliminating the need for them to travel to healthcare facilities. This research found that hospital pharmacists were unsure of their level of knowledge, their attitude toward telepharmacy, and their willingness to incorporate it into their future pharmacy practices. To ensure that tomorrow's pharmacists have the skills they need to provide telepharmacy services, telepharmacy practice models must be incorporated into the educational programs that prepare them.

Factors Associated with Length of Hospital Stay among COVID-19 Patients in Saudi Arabia: A Retrospective Study during the First Pandemic Wave.

The COVID-19 pandemic severely affected healthcare systems and tested their preparedness. To date, the length of hospital stay (LoHS) and its factors among COVID-19 patients has not been thoroughly studied. Moreover, it is essential to identify the features of these patients. Adult COVID-19 patients in Saudi Arabia with complete electronic medical records and who were hospitalised for >1 day between 1 May 2020 and 30 July 2020 at one of two hospitals were considered for this retrospective cohort study. Descriptive statistics and multivariate generalized linear models were performed using the data. Of the patients, 34% were ≥50 years old and 80.14% were female. More than 70% had mild-to-moderate symptoms; 45% had either diabetes or hypertension. The median LoHS was 7.00 days (IQR: 3−11). Patients who were females, had either critical or severe disease, were on mechanical ventilation, had diabetes, and administered ceftriaxone had significantly longer LoHS (p < 0.05). Patients administered zinc sulphate had significantly shorter LoHS (p = 0.0008). During the first pandemic wave, COVID-19 patients were hospitalised for 7 days. Healthcare professionals should pay more attention to women, patients with diabetes, and those with severe or critical symptoms. Unnecessary use of ceftriaxone should be minimised, and zinc sulphate can be administered.

A novel 5-Fluorocuracil multiple-nanoemulsion used for the enhancement of oral bioavailability in the treatment of colorectal cancer.

5-Fluorouracil (5-FU) is a drug of choice for colorectal-cancer. But oral therapeutic efficacy of 5-FU is restricted due to their very little bioavailability because of poor membrane permeability and GIT-absorption. We have developed a multiple nanoemulsion (w/o/w i.e. 5-FU-MNE) in which 5-FU incorporated to improve their oral-absorption. Globule-size of opt-5-FU-MNE was 51.64 ±â€¯2.61 nm with PDI and ZP 0.101 ±â€¯0.001 and -5.59 ±â€¯0.94, respectively. In vitro 5-FU-release and ex vivo permeation studies exhibited 99.71% release and 83.64% of 5-FU from opt-nanoformulation. Cytotoxic in vitro studies-exhibited that 5-FU in opt-5-FU-MNE was 5-times more potent than 5-FU-S on human-colon-cancer-cell-lines (HT-29). The enhanced Cmax with AUC0-8h with opt-5-FU-MNE was shown extremely significant (p < 0.001) in wistar rat's plasma in the comparison of oral and i.v. treated group of 5-FU-S by PK-observations. Furthermore, opt-5-FU-MNE was showed much more significant (p < 0.001) results as compared to 5-FU-S (free) on cell lines for human colon cancer (HT-29).

Comparison of the post-marketing safety profile between influenza and COVID-19 vaccines: An analysis of the vaccine adverse event reporting system.

The global coronavirus disease (COVID-19) epidemic can be partially managed by vaccines; however, the public must be informed about the safety of COVID-19 vaccines to avoid hesitancy. Therefore, it is important to know the safety profile of the COVID-19 vaccine by comparison to that of a well-known vaccine, such as the influenza vaccine. Hence, this retrospective descriptive study was conducted to evaluate and compare the number of adverse effects (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) for both COVID-19 and influenza vaccines, identify the most common AEs of each vaccine, and compare the frequency and outcomes of using COVID-19 and influenza vaccines in the U.S. population. Surveillance reports from 1st December 2020 to 8th October 2021 of both vaccines were retrieved from the U.S. VAERS. A total of 544,025 and 15,871 reports of post-COVID-19 and - influenza vaccine AEs were reported to the VAERS, respectively. Females reported > 58% and nearly 70% of influenza - and COVID-19 vaccine-associated AEs, respectively. The estimated incidence rates of AEs associated with COVID-19 and influenza vaccines in the U.S. were 1.36 and 0.12 per 1,000 persons, respectively. The incidence of AEs was higher among COVID-19 vaccine recipients than that among influenza vaccine recipients. COVID-19 vaccine recipients have a two-fold higher risk of mortality and life-threatening events than influenza vaccine recipients. However, most of the reported AEs were similar between the two vaccines in terms of symptoms.

Can First-Dose Therapeutic Drug Monitoring Predict the Steady State Area Under the Blood Concentration-Time Curve of Busulfan in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation?

Busulfan has high intra-individual variability and possible time-dependent changes in clearance, which complicates therapeutic drug monitoring (TDM), as first dose sampling may not predict the steady state concentrations. In this study, we aimed to use Bayesian pharmacokinetic parameters estimated from the first dose to predict the steady state AUC for busulfan. This observational study was conducted among pediatric patients at King Abdullah Specialist Children's Hospital. From each patient, we collected six blood samples (2, 2.25, 2.5, 3, 4, and 6 h after the start of IV infusion of the first dose). A subset of patients were also sampled at the steady state. First, we modeled the data using only the first dose. The model was used to estimate the empirical Bayesian estimates of clearance for each individual patient, then we used the empirical Bayesian estimates of clearance to predict the AUC0-tau at steady state (i.e., predicted AUC0-tau). Steady state AUC0-tau was also calculated for patients sampled at steady state using the trapezoidal method using raw time concentration data; this was considered the reference AUC0-tau.. Then, we compared the AUC0-tau predicted using the Bayesian approach with the reference AUC0-tau values. We calculated bias and precision to assess predictability. In total we had 33 patients sampled after first dose and at steady state. Using the Bayesian approach to predict the AUC0-tau, bias was -2.8% and precision was 33%. This indicates that first dose concentrations cannot accurately predict steady state busulfan concentrations; therefore, follow-up TDM may be required for optimal dosing.

Impact of Pharmacist-led Educational Intervention on Predictors of Diabetic Foot at Two Different Hospitals of Malaysia.

OBJECTIVE: Diabetes mellitus (DM) is a chronic metabolic disorder that can initiate organ damage inside the body if not treated appropriately. Apart from tight glycemic control, a suitable educational intervention is also needed from health-care providers to stop or decrease the progression of organ damage in diabetic patients. This study intended to measure the impact of pharmacist-led educational intervention on improvement in predictors of diabetic foot in two different hospitals in Malaysia. MATERIALS AND METHODS: In two tertiary care selected hospitals, the included diabetic patients were randomly divided into two study arms. In the control group, 200 patients who were receiving usual treatment from hospitals were included. However, in the intervention group, those 200 patients who were receiving usual treatment along with counseling sessions from pharmacists under the Diabetes Medication Therapy Adherence Clinic (DMTAC) program were included. The study continued for 1 year, and there were four follow-up visits for both study arms. A prevalidated data collection form was used to measure the improvement in predictors of diabetic foot in included patients. Data were analyzed by using the Statistical Package for the Social Sciences (SPSS) software program, version 24.0. RESULTS: With the average decrease of 1.97% of HbA1c values in the control group and 3.43% in the intervention group, the univariate and multivariate analysis showed a statistically significant difference between both of the study arms in the improvement of predictors belonging to the diabetic foot (P < 0.05). The proportion of patients without any signs and symptoms of the diabetic foot in the intervention group was 91.7%, which increased from 42.3% at baseline (P < 0.05). However, this proportion in the control group was 76.9% at the fourth follow-up, from 48.3% at baseline (P < 0.05). CONCLUSION: A statistically significant reduction in the signs and symptoms of diabetic foot was observed in the intervention group at the end of 1 year. The progression of diabetic foot was significantly decreased in the pharmacist intervention group.

The potential of drug-herbal interaction among patients with chronic diseases in Saudi Arabia.

AIMS: This study aimed to estimate the prevalence of the potential drug-herbal interaction among patients with chronic diseases in Al-Kharj, Saudi Arabia and to explore factors associated with the potential of drug-herbal interaction. METHOD: A cross-sectional study was conducted through interview-based questionnaire at outpatient clinics in Al-Kharj. The study included patients with chronic diseases who used herbal products. RESULTS: This study included 336 patients in total. The mean age of participants was 52.4 ± 12.0 years, and their most-used medications were metformin, atorvastatin, and aspirin, while their most-used herbs were ginger (74.7%), mint (72%), and cumin (66.7%). In 310 out of 336 (92.26%) cases, at least one potential drug-herbal interaction was found, and most of these interactions (84%) were moderate. CONCLUSION: A substantial percentage of potential drug-herbal interactions were found among patients with chronic diseases. Healthcare providers are encouraged to discuss the safety and efficacy of herbal products with their patients.

Population pharmacokinetics of busulfan in Saudi pediatric patients undergoing hematopoietic stem cell transplantation.

Background Busulfan is an antineoplastic drug that is used widely as part of a conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation. It has a narrow therapeutic index and highly variable pharmacokinetics; therefore therapeutic drug monitoring is recommended to optimize busulfan dosing. Objective To study the population pharmacokinetics of busulfan in Saudi pediatric patients to optimize its dosing. Settings King Abdullah Specialist Children's Hospital in Riyadh, Saudi Arabia. Methods This pharmacokinetic observational study was conducted between January 2016 and December 2018. All pediatric patients receiving IV busulfan and undergoing routine therapeutic drug monitoring were included. Population pharmacokinetics modeling was conducted using Monolix2019R1. Pharmacokinetic data of busulfan in children. Results The study included 59 patients and 513 samples. The mean ± SD age was 6.10 ± 3.17 years, and the dose administered was 0.994 ± 0.15 mg/kg. The mean ± SD Cmax and area under the curve (AUC) were 900.60 ± 402.8 ng/mL and 1031.14 ± 300.75 µM min, respectively. Based on our simulations, the European Medicines Agency recommended dose were adequate for most patient's groups to achieve the conventional target of an AUC0-tau of 900-1350 µM min. For patients in the lower weight group < 9 kg, higher doses were need at 1.2 mg/kg. With regards to the newly proposed target of AUC 78-101 mg h/mL, all of the doses we tested had low probability of achieving it. Conclusions Most of our patients had less than a proportional increase in busulfan concentration suggesting autoinduction. The high interindividual variability and autoinduction make dose adjustments challenging and AUC at steady state difficult to predict from the first dose. One approach to improve dose predictions is to use Bayesian dosing software. Based on our simulations, the European Medicines Agency recommended doses were adequate for most patient groups, except those in the lower (< 9 kg) and higher weight groups (> 34 kg).

The Relationship Between Health-Related Quality of Life and Trust in Primary Care Physicians Among Patients with Diabetes.

BACKGROUND: Trust is pivotal for a productive relationship between patients and healthcare providers and is positively correlated with multiple clinical and humanistic outcomes. However, the impact of trust in healthcare providers on different domains of health-related quality of life (HRQoL) among diabetic patients has not been studied in detail. PURPOSE: The aim of this study was to examine the association between the physical, mental or psychological, social, and environmental domains of HRQoL with the patients' trust in their primary care physicians while controlling for several sociodemographic and clinical factors. The study was conducted among a sample of diabetic patients. PATIENTS AND METHODS: This study had a prospective questionnaire-based, multi-center, cross-sectional design. The patients were recruited from three public hospitals in Saudi Arabia. Patients' experiences and trust in their primary care physicians were assessed using the Health Care Relationship Trust (HCR-Trust) scale. HRQoL was assessed using the Arabic version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF). Multiple linear regression was conducted to assess the relationship between HCR-Trust and the WHOQOL-BREF physical, psychological, social, and environmental domains controlling for age, Charlson Comorbidity Index (CCI) score, health literacy, sex, education, annual income, nationality, and illness duration. RESULTS: Three hundred and sixty-four patients participated in the study. The scores in all four domains of WHOQOL-BREF were positively associated with HCR-Trust scores of the diabetic patients. Additionally, the scores in the physical (ß = -10.26; 95% CI: -13.77 to -6.74; P < 0.0001) and psychological (ß = -3.91; 95% CI: -7.44 to -0.38; P < 0.0001) domains were negatively associated with female gender. Furthermore, the physical domain score was negatively associated with the duration of illness (ß = -0.26; 95% CI: -0.506 to -0.02; P = 0.032). The environmental domain score was positively associated with annual income (ß = 2.31; 95% CI: 1.05 to 3.56; P = 0.030). Other patient characteristics, such as age and education, were not associated with the scores of any of the WHOQOL-BREF domains. CONCLUSION: Patient trust in healthcare providers is positively associated with different domains of HRQoL. Therefore, building and maintaining trust with patients is important to achieve favorable treatment outcomes.

Knowledge of the Use of Herbal Medicines among Community Pharmacists and Reporting Their Adverse Drug Reactions.

INTRODUCTION: Community pharmacist's knowledge about the uses of herbal medicines and its adverse drug reactions reporting can contribute in better therapeutic outcomes and patient safety. Objectives: To evaluate community pharmacists' knowledge about the use of herbal medicines and its adverse drug reactions reporting in Kedah state, Malaysia. METHODS: A cross-sectional, questionnaire-based study was conducted among 103 pharmacists from 74 different community pharmacies to assess their knowledge about the use of herbal medicines and its adverse drug reaction reporting by using a pre-validate knowledge questionnaire consisting of 12 questions related to it. The pharmacists' responses were measured at a 3-point Likert scale (Poor=1, Moderate=2, and Good=3) and data was entered in SPSS version 22. The minimum and maximum possible scores for knowledge questionnaires were 12 and 36 respectively. Quantitative data was analyzed by using One Way ANOVA and Paired t-test whereas Chi-square and Fisher exact test were used for qualitative data analysis. A p-value of less than 0.05 was considered statistically significant for all the analyses. RESULTS: About 92% of the pharmacist had good knowledge regarding the use of herbal medicines and its adverse drug reaction reporting with a mean knowledge score of 32.88±3.16. One-way ANOVA determined a significant difference of employment setting (p<0.043) and years of experience (<0.008) with mean knowledge scores of Pharmacists. Pharmacists' knowledge was significantly associated with their years of experience with the Chi-square test. CONCLUSION: Pharmacists exhibit good knowledge regarding the use of herbal medicines and its adverse drug reaction reporting. However, with an increasing trend of herbal medicine use and its adverse drug reaction reporting it recalls the empowerment of experienced pharmacists with training programs in this area for better clinical outcomes.

Effect of pterostilbene on in vitro drug metabolizing enzyme activity.

Pterostilbene is a natural polyphenol compound found in small berries that is related to resveratrol, but has better bioavailability and a longer half-life. The purpose of this study was to assess the potential inhibitory effect of pterostilbene on in vitro drug metabolism. The effect of pterostilbene on cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzyme activities were studied using the enzyme-selective substrates amodiaquine (CYP2C8), midazolam (CYP3A4), estradiol (UGT1A1), serotonin (UGT1A6) and mycophenolic acid (UGT1A8/9/10). The IC50 value was used to express the strength of inhibition. Further, a volume per dose index (VDI) was used to estimate the potential for in vivo interactions. Pterostilbene significantly inhibited CYP2C8 and UGT1A6 activities. The IC50 (mean ±â€¯SE) values for CYP2C8 and UGT1A6 inhibition were 3.0 ±â€¯0.4 µM and 15.1 ±â€¯2.8 µM, respectively; the VDI exceeded the predefined threshold of 5 L/dose for both CYP2C8 and UGT1A6, suggesting a potential for interaction in vivo. Pterostilbene did not inhibit the metabolism of the other enzyme-selective substrates. The results of this study indicate that pterostilbene inhibits CYP2C8 and UTG1A6 activity in vitro and may inhibit metabolism by these enzymes in vivo. Clinical studies are warranted to evaluate the in vivo relevance of these interactions.

Inhibition of cytochrome P450 enzymes by thymoquinone in human liver microsomes.

The aim of the present study was to investigate the potential effect of thymoquinone (TQ) on the metabolic activity of four major drug metabolizing enzymes in human liver microsomes, namely cytochrome P450 (CYP) 1A2, CYP2C9, CYP2D6 and CYP3A4. The inhibition of CYP enzymatic activities by TQ was evaluated by incubating typical substrates (phenacetin for CYP1A2, tolbutamide for CYP2C9, dextromethorphan for CYP2D6, and testosterone for CYP3A4) with human liver microsomes and NADPH in the absence or presence of TQ (1, 10 and 100 µM). The respective metabolite of the substrate that was formed was measured by HPLC. Results of the presented study presented that the metabolic activities of all the investigated CYP enzymes, viz. CYP1A2, CYP2C9, CYP2D6 and CYP3A4, were inhibited by TQ. At 1 µM TQ, CYP2C9 enzyme activity was maximally inhibited by 46.35%, followed by CYP2D6 (20.26%) > CYP1A2 (13.52%) > CYP3A4 (12.82%). However, at 10 µM TQ, CYP2C9 enzyme activity was maximally inhibited by 69.69%, followed by CYP3A4 (23.59%) > CYP1A2 (23.51%) > CYP2D6 (11.42%). At 100 µM TQ, CYP1A2 enzyme activity was maximally inhibited by 81.92%, followed by CYP3A4 (79.24%) > CYP2C9 (69.22%) > CYP2D6 (28.18%). The IC50 (mean ±â€¯SE) values for CYP1A2, CYP2C9, CYP2D6 and CYP3A4 inhibition were 26.5 ±â€¯2.9 µM, 0.5 ±â€¯0.4 µM, >500 µM and 25.2 ±â€¯3.1 µM, respectively. These findings suggest that there is a high probability of drug interactions resulting from the co-administration of TQ or herbs containing TQ with drugs that are metabolized by the CYP enzymes, particularly CYP2C9.

The effect of milk thistle (Silybum marianum) and its main flavonolignans on CYP2C8 enzyme activity in human liver microsomes.

Milk thistle is a widely-consumed botanical used for an array of purported health benefits. The primary extract of milk thistle is termed silymarin, a complex mixture that contains a number of structurally-related flavonolignans, the flavonoid, taxifolin, and a number of other constituents. The major flavonolignans present in most extracts are silybin A, silybin B, isosilybin A and isosilybin B, silydianin, silychristin and isosilychristin. Silymarin itself has been reported to inhibit CYP2C8 activity in vitro, but the effect of the individual flavonolignans on this enzyme has not been studied. To investigate the effects of milk thistle extract and its main flavonolignans (silybin A, silybin B, isosilybin A and isosilybin B) on CYP2C8 activity at relevant concentrations, the effect of milk thistle extract and the flavonolignans on CYP2C8 enzyme activity was studied in vitro using human liver microsomes (HLM) incorporating an enzyme-selective substrate for CYP2C8, amodiaquine. Metabolite formation was analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS). The concentration causing 50% inhibition of enzyme activity (IC50) was used to express the degree of inhibition. Isosilibinin, a mixture of the diastereoisomers isosilybin A and isosilybin B, was found to be the most potent inhibitor, followed by isosilybin B with IC50 values (mean ± SE) of 1.64 ± 0.66 µg/mL and 2.67 ± 1.18 µg/mL, respectively. The rank order of observed inhibitory potency after isosilibinin was silibinin > isosilybin A > silybin A > milk thistle extract > and silybin B. These in vitro results suggest a potentially significant inhibitory effect of isosilibinin and isosilybin B on CYP2C8 activity. However, the observed IC50 values are unlikely to be achieved in humans supplemented with orally administered milk thistle extracts due to the poor bioavailability of flavonolignans documented with most commercially available formulations.