Background: The global increase in type 2 diabetes mellitus (DM2) and obesity presents a significant public health challenge, as these interconnected conditions contribute to severe complications, including cardiovascular disease, stroke, and certain cancers. The incretin system, particularly glucagon-like peptide-1 (GLP-1), has emerged as a promising therapeutic target due to its role in glycemic control and weight management. Objective: This review explores the molecular pharmacology of GLP-1 and its receptor agonists, evaluating their therapeutic efficacy in managing DM2 and obesity. Methods: A comprehensive literature review was conducted, analyzing recent advancements in GLP-1-based therapies, their mechanisms of action, and their clinical applications. The review also highlights the pharmacokinetic modifications developed to enhance the stability and efficacy of GLP-1 receptor agonists. Results: GLP-1 receptor agonists have demonstrated significant benefits in improving glycemic control, reducing body weight, and addressing metabolic complications. Novel therapeutic approaches, including dual and triple incretin receptor agonists, are showing enhanced efficacy in both diabetes and obesity management. However, challenges remain in optimizing treatment outcomes, addressing patient variability, and improving long-term adherence. Conclusion: GLP-1-based therapies have revolutionized the management of DM2 and obesity. Continued research is essential to refine these treatments, overcome existing limitations, and develop personalized approaches to maximize patient outcomes.
The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0–24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½β, and the first-order rate constant for the elimination process β in FN compared to non-FN patients. Furthermore, AUC0–24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0–24, which may require specific consideration during the treatment initiation.
Vancomycindosing error and inappropriate monitoring is a common problem in hospital daily practice. In King Abdulaziz Medical City (KAMC) in Jeddah, a high percentage of abnormal vancomycin trough levels is still detected despite using the recommended dose. Therefore, the current research objective is to study the major causes of vancomycin dosing errors. This retrospective, single-center, cross-sectional study was carried out at KAMC hospital in Jeddah from January 1st until December 31st 2019. All adult patients (≥15 years) who received vancomycin and had an initial abnormal trough level at the measured steady-state were included in this study. 472 patients have met the study inclusion criteria.
Introduction: Vancomycin administration in individuals with hematological malignancy or neutropenia is associated with a suboptimal trough concentration. Nonetheless, most studies did not distinguish whether low vancomycin trough concentrations were due to hematological malignancies or neutropenia. This study aimed to determine the association between types of hematological malignancy and febrile neutropenia with low vancomycin concentrations. Methods: The present retrospective chart review study was conducted by using clinical data adopted from computerized physician order entries (BestCare®) for all of the patients who received intravenous vancomycin treatment between January 2017 and December 2020 at King Abdulaziz Medical City in Jeddah. Results: Out of the 296 patients, 217 were included. There was no significant association between the type of hematological malignancy and the incidence of a low trough concentration (p > 0.05), while a significant association between febrile neutropenia and the incidence of a low trough concentration was observed (p < 0.05). Furthermore, the predictors for a low trough among febrile neutropenic patients were creatinine clearance (CrCI) and a low albumin concentration. In addition, there was a significant association between febrile neutropenia and augmented renal clearance (p < 0.05). Conclusions: The findings of this study conclude that febrile neutropenia is associated with low vancomycin concentrations. Interestingly, augmented renal clearance was observed in most of the febrile neutropenia patients with a significant association, which is considered the main driver for a low trough in neutropenic patients.
The AUC0–24 is the most accurate way to track the vancomycin level while the Cmin is not an accurate surrogate. Most hospitals in Saudi Arabia are under-practicing the AUC-guided vancomycin dosing and monitoring. No previous work has been conducted to evaluate such practice in the whole kingdom. The current study objective is to calculate the AUC0–24 using the Bayesian dosing software (PrecisePK), identify the probability of patients who receive the optimum dose of vancomycin, and evaluate the accuracy and precision of the Bayesian platform. This retrospective study was conducted at King Abdulaziz medical city, Jeddah. All adult patients treated with vancomycin were included. Pediatric patients, critically ill patients requiring ICU admission, patients with acute renal failure or undergoing dialysis, and febrile neutropenic patients were excluded. The AUC0–24 was predicted using the PrecisePK platform based on the Bayesian principle. The two-compartmental model by Rodvold et al. in this platform and patients’ dose data were utilized to calculate the AUC0–24 and trough level. Among 342 patients included in the present study, the mean of the estimated vancomycin AUC0–24 by the posterior model of PrecisePK was 573 ± 199.6 mg, and the model had a bias of 16.8%, whereas the precision was 2.85 mg/L. The target AUC0–24 (400 to 600 mg·h/L) and measured trough (10 to 20 mg/L) were documented in 127 (37.1%) and 185 (54%), respectively. Furthermore, the result demonstrated an increase in odds of AUC0–24 > 600 mg·h/L among trough level 15–20 mg/L group (OR = 13.2, p < 0.05) as compared with trough level 10–14.9 mg/L group. In conclusion, the discordance in the AUC0–24 ratio and measured trough concentration may jeopardize patient safety, and implantation of the Bayesian approach as a workable alternative to the traditional trough method should be considered.
Introduction Most computerized physician order entry (CPOE) software come with clinical decision-support components (CDS) that provide prescribers assistance and notify them about adverse drug reactions. An excessive number of alerts in a repeated and non-relevant manner leads to alert fatigue and enforces physicians and pharmacists to alert overrides. King Abdulaziz Medical City (KAMC) in Jeddah still reports a higher percentage of drug alerts overridden by clinicians and pharmacists. Thus, this study was conducted to evaluate CDS alerts overriding and to determine which alerts are clinically irrelevant and need modifications. Methods The study was carried out in the inpatient setting at KAMC in Jeddah, from September 1, 2020, to December 31, 2020. It was designed as a retrospective chart review study that included all red alerts that required comments and were overridden by a physician and pharmacist. Results Among 11350 red alerts, potential drug-drug interaction (pDDI), dose, and allergy alerts represent 57%, 41%, and 2%, respectively, of the total alerts. The most common drug-drug interactions (DDIs) in category X were proton pump inhibitors and clopidogrel (9.9%). The appropriate response by prescribers and pharmacists toward allergy alerts was associated with the highest odds compared with the other alerts (p < 0.05) while there is a significant decrease in the odds of appropriate action being taken by both prescribers and pharmacists in the dose screen alerts (p < 0.05). Among all clinical specialties, there is an increased odds of appropriate action being taken by residents and fellows for allergy and dose alerts, respectively, compared to other groups (p < 0.05). For diminishing the unnecessary alerts, we provided 14 alert refinements strategies and advised turning off four alerts. Applying this will terminate 32% of irrelevant alerts. Conclusion Our study's findings indicated that a substantial number of alerts are ignored, and the rate of appropriateness varies significantly by alert type and prescriber level.