Evaluation of in vitro dissolution profiles of modified-release metoprolol succinate tablets crushed using mortar and pestle technique.

PURPOSE: Clinical practice guidelines advise against crushing modified-release dosage forms. Metoprolol succinate modified-release (MS-MR) tablets are commonly crushed in clinical practice to facilitate administration to patients with swallowing difficulties or using feeding tubes. To date, the effect of this practice remains unexplored. The in vitro effects of crushing commercially available MS-MR tablets were explored using a holistic approach. METHODS: Dissolution profiles of crushed versus whole MS-MR tablets were compared. Tablets were crushed to powder state using pragmatic method mimicking hospital practices. For standardization purposes, the same operator, duration (60 seconds), hand, and mortar-pestle apparatus were used. Dissolution studies were conducted per U.S. Pharmacopeia at pH 1.2, pH 4.5, and pH 6.8 with USP apparatus 2 (paddle) at rotation speed of 50 rpm at 37±0.5 °C in 500 mL dissolution media. Samples were withdrawn at predetermined time points. Percent drug dissolved was measured by validated UV-vis Spectrophotometry. Comprehensive analysis of the dissolution data was conducted using model-independent, model-dependent, and ANOVA-based approaches (SPSS v.23 at α=0.05). Similarity (f2) and difference (f1) factors were calculated to compare the dissolution profiles between crushed (CT) and whole tablets (WT). Goodness of fit (GOF) analysis examined the compliance between in vitro dissolution behaviors and several drug release models. Model selection was based on GOF plots, Akaike criteria and adjusted coefficient of determination (R2adj). Imaging and particle size distribution analysis were conducted to examine associated surface and morphologic changes. RESULTS: The dissolution profiles were not similar at pH 4.5 (f2=45.43, f1=18.97) and pH 6.8 (f2=31.47, f1=32.94). CT best fitted with Higuchi (pH 1.2: R2adj=0.9990), Weibull (pH 4.5: R2adj=0.9884), and Korsmeyer-Peppas (pH 6.8: R2adj=0.9719). Contrastingly, WT best fitted with Hopfenberg (pH 1.2: R2adj=0.9986), logistic (pH 4.5: R2adj=0.9839) and first-order (pH 6.8: R2adj=0.9979) models. A significant difference in the dissolution profiles was found between CT and WT using multivariate analysis of variance per time points and between the tablet forms (p=0.004). This was confirmed by unparalleled dissolution profiles. Crushing resulted in variations in particle size and surface morphological changes to the micropellets. CONCLUSION: Crushing practices change the dissolution profile of MS-MR tablets by deforming the surface morphology of embedded micropellets. Amounts of drug dissolved between CT and WT were not the same at the compared time points across gastrointestinal pH ranges. This suggests potential clinical impact on plasma-concentration profiles of critically ill patients using feeding tube.

Continuing Professional Development Needs of Community Pharmacists in Qatar: A Mixed-Methods Approach.

OBJECTIVE: This study aims to assess the educational needs and professional competencies of community pharmacists in Qatar to inform the development of relevant continuing professional development (CPD) programs. METHODS: A mixed-methods cross-sectional exploratory study targeting community pharmacists was conducted using a questionnaire and an event diary. Descriptive and inferential analyses were utilized to analyze the data using the Statistical Package for Social Sciences (SPSS®) version 21 software. For the event diary, thematic content analysis was used for data analysis. RESULTS: Drug information skills and pharmaceutical care process were the most identified topics for inclusion in CPD programs. None of the pharmacists thought that they were competent in core areas of pharmacy practice. Community pharmacists who filled an event diary highlighted the need for development in areas such as communication skills and medication safety. CONCLUSION: The identified needs shall help in developing a CPD program that addresses what community pharmacists perceive as educational and professional training needs.

Clinical and Pharmacokinetic Outcomes of Peak-Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial.

BACKGROUND: Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration-time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. OBJECTIVES: We aimed to compare clinical and pharmacokinetic outcomes between peak-trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. METHODS: A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak-trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. RESULTS: Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak-trough-based-TDM (n = 30)]. Peak-trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak-trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak-trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak-trough-based group. CONCLUSION: Maintenance of target vancomycin exposures and implementation of peak-trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.

Evaluating community pharmacy practice in Qatar using simulated patient method: acute gastroenteritis management

Objective: To evaluate Qatari pharmacists’ prescribing, labeling, dispensing and counseling practices in response to acute community-acquired gastroenteritis. Methods: The simulated patient method was used in this study. Thirty pharmacies in Doha were randomly selected and further randomized into two groups: Face-to-Face (n=15) vs. Telephone-call (n=15) per simulated patient; 2 simulated patients were involved. Prescribing, labeling, dispensing and counseling practices were assessed. Data analysis was performed using Mann-Whitney and chi square tests at alpha=0.05. Results: Most pharmacists prescribed and dispensed medicines (96%), including antimicrobials (43.9%), antidiarrheals (36%), antiemetics (5.1%) and antipyretics (3%). Counseling practices were poor (62.1% in the face-to-face group vs 70% in the telephone-call group did not counsel simulated patients about the dispensed medicines; p-value=0.50). In more than one-third of the encounters, at least one labeling parameter was missing. The duration of each interaction in minutes was not significantly different between the groups [median (IQR); 3(4.25) in the face-to-face group versus 2(0.25) in the telephone-call group; p-value=0.77]. No significant differences in prescribing or dispensing behaviors were present between groups (p-value>0.05). Conclusion: Qatar community pharmacists’ labeling, dispensing, and counseling practices were below expectation, thus urging the need for continuous professional development (AU)

No disponible

Evaluating community pharmacy practice in Qatar using simulated patient method:acute gastroenteritis management.

OBJECTIVE: To evaluate Qatari pharmacists' prescribing, labeling, dispensing and counseling practices in response to acute community-acquired gastroenteritis. METHODS: The simulated patient method was used in this study. Thirty pharmacies in Doha were randomly selected and further randomized into two groups: Face-to-Face (n=15) vs. Telephone-call (n=15) per simulated patient; 2 simulated patients were involved. Prescribing, labeling, dispensing and counseling practices were assessed. Data analysis was performed using Mann-Whitney and chi square tests at alpha=0.05. RESULTS: Most pharmacists prescribed and dispensed medicines (96%), including antimicrobials (43.9%), antidiarrheals (36%), antiemetics (5.1%) and antipyretics (3%). Counseling practices were poor (62.1% in the face-to-face group vs 70% in the telephone-call group did not counsel simulated patients about the dispensed medicines; p-value=0.50). In more than one-third of the encounters, at least one labeling parameter was missing. The duration of each interaction in minutes was not significantly different between the groups [median (IQR); 3(4.25) in the face-to-face group versus 2(0.25) in the telephone-call group; p-value=0.77]. No significant differences in prescribing or dispensing behaviors were present between groups (p-value>0.05). CONCLUSION: Qatar community pharmacists' labeling, dispensing, and counseling practices were below expectation, thus urging the need for continuous professional development.

Na+/H+ exchanger isoform 1 induced cardiomyocyte hypertrophy involves activation of p90 ribosomal s6 kinase.

Studies using pharmacological and genetic approaches have shown that increased activity/expression of the Na+/H+ exchanger isoform 1 (NHE1) play a critical role in the pathogenesis of cardiac hypertrophy. Despite the importance of NHE1 in cardiac hypertrophy, severe cerebrovascular side effects were associated with the use of NHE1 inhibitors when administered to patients with myocardial infarctions. p90 ribosomal S6 Kinase (RSK), a downstream regulator of the mitogen-activated protein kinase pathway, has also been implicated in cardiac hypertrophy. We hypothesized that RSK plays a role in the NHE1 induced cardiomyocyte hypertrophic response. Infection of H9c2 cardiomyoblasts with the active form of the NHE1 adenovirus induced hypertrophy and was associated with an increase in the phosphorylation of RSK (P<0.05). Parameters of hypertrophy such as cell area, protein content and atrial natriuretic mRNA expression were significantly reduced in H9c2 cardiomyoblasts infected with active NHE1 in the presence of dominant negative RSK (DN-RSK) (P<0.05). These results confirm that NHE1 lies upstream of RSK. Increased phosphorylation and activation of GATA4 at Ser261 was correlated with increased RSK phosphorylation. This increase was reversed upon inhibition of RSK or NHE1. These findings demonstrate for the first time that the NHE1 mediated hypertrophy is accounted for by increased activation and phosphorylation of RSK, which subsequently increased the phosphorylation of GATA4; eventually activating fetal gene transcriptional machinery.