Background: In addition to the maximum plasma concentration (C_max) to the minimum inhibitory concentration (MIC) ratio, the 24-hour area under the concentration-time curve (AUC_24h) to MIC has recently been suggested as pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy and safety in once-daily dosing of gentamicin (ODDG) in critically ill patients. Purpose: This study aimed to predict the optimal effective dose and risk of nephrotoxicity for gentamicin in critically ill patients for two different PK/PD targets within the first 3 days of infection. Methods: The gathered pharmacokinetic and demographic data in critically ill patients from 21 previously published studies were used to build a one-compartment pharmacokinetic model. The Monte Carlo Simulation (MCS) method was conducted with the use of gentamicin once-daily dosing ranging from 5– 10 mg/kg. The percentage target attainment (PTA) for efficacy, C_max/MIC ~8– 10 and AUC_24h/MIC ≥ 110 targets, were studied. The AUC_24h > 700 mg⋅h/L and C_min > 2 mg/L were used to predict the risk of nephrotoxicity. Results: Gentamicin 7 mg/kg/day could achieve both efficacy targets for more than 90% when the MIC was < 0.5 mg/L. When the MIC increased to 1 mg/L, gentamicin 8 mg/kg/day could reach the PK/PD and safety targets. However, for pathogens with MIC ≥ 2 mg/L, no studied gentamicin doses were sufficient to reach the efficacy target. The risk of nephrotoxicity using AUC_24h > 700 mg⋅h/L was small, but the risk was greater when applying a C_min target > 2 mg/L. Conclusion: Considering both targets of Cmax/MIC ~8– 10 and AUC_24h/MIC ≥ 110, an initial gentamicin dose of 8 mg/kg/day should be recommended in critically ill patients for pathogens with MIC of ≤ 1 mg/L. Clinical validation of our results is essential.

Purpose: Serum digoxin concentration (SDC) monitoring may be unavailable in some healthcare settings. Predicted SDC comes into play in the efficacy and toxicity monitoring of digoxin. Renal function is the important parameter for predicting SDC. This study was conducted to compare measured and predicted SDC when using creatinine clearance (CrCl) from Cockcroft–Gault (CG) equation and estimated glomerular filtration rate (eGFR) calculated from CKD-Epidemiology Collaboration (CKD-EPI), re-expressed Modification of Diet in Renal Disease (Re-MDRD4), Thai-MDRD4, and Thai-eGFR equations in Sheiner’s and Konishi’s pharmacokinetic models. Patients and methods: In this retrospective study, patients with cardiovascular disease with a steady-state of SDC within 0.5–2.0 mcg/L were enrolled. CrCl and studied eGFR adjusted for body surface area (BSA) were used in the models to determine the predicted SDC. The discrepancies of the measured and the predicted SDC were analyzed and compared. Results: One hundred and twenty-four patients ranging in age from 22 to 88 years (median 60 years, IQR 50.2, 69.2) were studied. Their serum creatinine ranged from 0.40 to 1.80 mg/dL (median 0.90 mg/dL, IQR 0.79, 1.10). The mean±SD of measured SDC was 1.12±0.34 mcg/L. In the Sheiner’s model, the mean predicted SDC was calculated by using the CG and the BSA adjusted CKD-EPI equations and was not different when compared with the measured levels (1.10±0.36 mcg/L (p=0.669) and 1.08±0.42 mcg/L (p=0.374), respectively). The CG, CKD-EPI, and Re-MDRD4 equations were a better fit for patients with creatinine ≥0.9 mg/dL for prediction with minimal errors. In the Konishi’s model, the predicted SDC using the CG and the studied eGFR equation was lower than the measured SDC (p<0.05). Conclusion: In Sheiner’s model, the CG and the BSA adjusted CKD-EPI equations should be used for predicting SDC, especially in patients with serum creatinine ≥0.9 mg/dL. The other studied eGFRs underestimated SDC in both Sheiner’s and Konishi’s model.

Background: Hypomagnesemia is common for surgical patients and often requires intravenous (IV) magnesium replacement. Due to the renal handling mechanism of magnesium, prolonging the duration of an IV magnesium infusion has been postulated to improve magnesium retention by reducing the renal excretion of magnesium. However, the evidence supporting this hypothesis is limited. Objective: To determine the change in serum magnesium level after IV magnesium replacement from baseline compared between prolonged (infusion rate < 0.5 g/h) and short infusions (infusion rate < 0.5 g/h) in hospitalized surgical patients. Methods: Medical records of surgical patients with hypomagnesemia who received IV magnesium replacement for three consecutive days and admitted to a university hospital between 2012 and 2022 were reviewed. Patients were separated by the replacement rate into two cohorts: prolonged infusion and short infusion. The primary outcome was a change in serum magnesium per gram administered from the baseline. The secondary outcome was the percentage of patients who achieved an optimal serum magnesium level after IV magnesium replacement. Results: 114 participants were enrolled in the study. The short infusion cohort showed a significantly greater increase in serum magnesium change per gram administered from baseline (0.07 mg/dL/g) compared to the prolonged infusion cohort (0.05 mg/dL/g) (p = 0.04). The difference of serum magnesium level between the two cohorts was 0.013 mg/dL/g of Mg. The percentage of patients who achieved the optimal serum magnesium level after IV magnesium replacement was not different between the two cohorts (prolonged infusion 66.7% vs. short infusion 70.2%; p = 0.84). The change in serum magnesium levels was influenced by renal function and the timing of serum magnesium level measurement after IV magnesium replacement. Conclusion: In hospitalized surgical patients, prolonging the IV magnesium infusion rate to less than 0.5 g/h did not provide additional benefits to increase serum magnesium levels compared to a short infusion rate.

Background: The appropriate dose of gentamicin is important to prevent and treat infections. The study aimed to determine the optimal dose of gentamicin to achieve the probability of pharmacokinetic/pharmacodynamic (PK) targets for efficacy and safety in multiple trauma patients. Methods: PK parameters of gentamicin in multiple trauma patients were gathered to develop a one-compartment PK model for prediction. The Monte Carlo simulation method was performed. The 24-h area under the concentration time curve to the minimum inhibitory concentration ratio (AUC24h/MIC) ≥50 was defined for the infection prevention target. AUC24h/MIC ≥110 or the maximum serum concentration to MIC ratio ≥8–10 was for the treatment of serious Gram-negative infection target. The risk of nephrotoxicity was the minimum serum concentration ≥2 mg/L. The optimal dose of gentamicin was determined when the efficacy target was >90% and the risk of nephrotoxicity was lowest. Results: The optimal gentamicin dose to prevent infection when the MIC was <1 mg/L was 6–7 mg/kg/day. A higher dose of gentamicin up to 10 mg/kg/day could not reach the target for treating serious Gram-negative infection when the expected MIC was ≥1 mg/L. The probability of nephrotoxicity was minimal at 0.2–4% with gentamicin doses of 5–10 mg/kg/day for 3 days. Conclusions: Once daily gentamicin doses of 6–7 mg/kg are recommended to prevent infections in patients with multiple trauma. Gentamicin monotherapy could not be recommended for serious infections. Further clinical studies are required to confirm our results.

The U.S.-Thai Consortium for Pharmacy Education is a long-standing collaboration between the U.S. and Thailand that primarily focuses on faculty development. The success of this partnership has contributed to the improvement of pharmacy education and the advancement of pharmacy practice in Thailand. It may also serve as a model for collaborative efforts in pharmacy education and practice across Association of Southeast Asian Nations (ASEAN) countries. This study was designed to explore the views and perceptions on goals, directions, and trends for the new U.S.- ASEAN Consortium for Pharmacy Education. A qualitative study was used. A focus group with semi-structured questions was conducted with 12 representative faculty members from nine ASEAN countries and the U.S. Verbatim transcriptions were used to perform thematic analysis with investigator triangulation. Four key themes emerged: perceptions, challenges, expectations, and directions. Participants perceived the U.S.-ASEAN Consortium as a strategic networking platform for expanding international collaborations. Challenges were identified at both the institutional and national levels, with curriculum differences, financial constraints, and administrative issues affecting institutions, while cultural and language differences pose further obstacles. At the national level, top-down administrative structures were identified as restrictions. The main expressed benefit of joining the Consortium was enhancement of student experiences, including student exchange programmes. Gaining insights into organisational administration was also perceived as one of the benefits. Participants recognised that a successful collaboration required identifying common interests, setting goals, and proposing strategies, including developing a master plan, harmonising programmes, and establishing a uniform competency framework. Regular meetings and resource-sharing were identified as also essential to maintaining the engagement of Consortium members. The U.S.-ASEAN Consortium was perceived as a platform to increase opportunities to collaboratively connect with other pharmacy schools internationally. The establishment of common interests and strategies was recommended to keep the collaboration moving forward.