Intracoronary versus intravenous glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in patients with STEMI: a systematic review and meta-analysis

Background Intracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI. Methods We searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included. Results The proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37–0.80) and heart failure (RR: 0.48, 95% CI: 0.25–0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration. Conclusions When considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considere

Population pharmacokinetics of everolimus in patients with seizures associated with focal cortical dysplasia

Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type Ⅱ (FCD Ⅱ) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed.Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States).Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5–15 ng/mL.Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg

Effect of Multi-Dose Dispensing on Medication Regimen Complexity: A Real-World Study

(1) Background: Older patients frequently require dosing aids, such as multi-dose medication dispensing (MMD) when they experience medication regimen complexity (MRC) with increased drug use. However, the evaluations of the efficacy of MMD alterations remain limited. (2) Methods: A total of 1120 patients were included in the study who were discharged from hospital during the study period of January to March 2019. The Medication Regimen Complexity Index (MRCI) score, a validated 65-item tool in Korea (MRCI-K), was used to quantify MRC. The original MRCI-K scores, representing the typical administration based on prescription information, were compared to recalculated MRCI-K scores measured following MMD during the hospital dispensing period. Differences in MRCI-K across the top four wards based on the numbers of discharge prescription medications were assessed, and the overall scores were categorized into quartiles to identify MMD’s impact within each group. We confirmed the effect of MMD based on the patient’s admission diagnosis depending on MRCI. (3) Results: The mean (standard deviation) of original MRCI scores was 26.2 (13.4), which decreased to 18.9 (8.8) after applying MMD. The decrease in MRCI scores after MMD was statistically significant in all four wards, with the Orthopedic Surgery ward showing the biggest decrease. The patients with MRCI scores in the highest quartile group demonstrated the greatest improvement as a result of the implementation of MMD. Respiratory diseases exhibited the highest baseline MRCI scores due to formulation complexity, and ear, nose, and throat patients demonstrated the most significant reduction in MRC after MMD, depending on the diagnostic criteria at administration. (4) Conclusions: We confirmed the reduction in MRC after applying MMD, as a significant decrease in MRCI-K scores. This study highlights the need to deliver effective pharmacist-led services to identify patients who would benefit from MMD

Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling

Background: Our objective was to determine an optimal dosage regimen of meropenem in patients receiving veno-arterial extracorporeal membrane oxygenation (V-A ECMO) by developing a pharmacokinetic/pharmacodynamic (PK/PD) model. Methods: This was a prospective cohort study. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF). The population pharmacokinetic model was developed using nonlinear mixed-effects modeling. A Monte Carlo simulation was used (n = 10,000) to assess the probability of target attainment. Results: Thirteen adult patients on ECMO receiving meropenem were included. Meropenem pharmacokinetics was best fitted by a two-compartment model. The final pharmacokinetic model was: CL (L/h) = 3.79 × 0.44CRRT, central volume of distribution (L) = 2.4, peripheral volume of distribution (L) = 8.56, and intercompartmental clearance (L/h) = 21.3. According to the simulation results, if more aggressive treatment is needed (100% fT > MIC target), dose increment or extended infusion is recommended. Conclusions: We established a population pharmacokinetic model for meropenem in patients receiving V-A ECMO and revealed that it is not necessary to adjust the dosage depending on V-A ECMO. Instead, more aggressive treatment is needed than that of standard treatment, and higher dosage is required without continuous renal replacement therapy (CRRT). Also, extended infusion could lead to better target attainment, and we could provide updated nomograms of the meropenem dosage regimen

Development and validation of the Korean version of the medication regimen complexity index.

The medication regimen complexity index (MRCI), originally developed in English, is a reliable and valid tool to assess the complexity of pharmacotherapy. This study aimed to validate the Korean version of MRCI (MRCI-K). A cross-cultural methodological study comprising 335 discharged patients of a tertiary hospital in Korea was conducted. The translation process included translation into Korean by two clinical pharmacists, back translation by two native speakers, and a pretest of the tool, culminating in the Korean version of MRCI-K. Reliability analysis was assessed using inter-rater and test-retest reliability with 25 randomly selected patients. Convergent and discriminant validity analyses were conducted by correlating MRCI scores with medication number, age, sex, adverse drug reaction (ADR) reports, and length of stay. The criterion validity was confirmed through evaluation by a nine-member expert panel that subjectively ranked these regimens. The reliability analysis demonstrated excellent internal consistency (Cronbach's α = 0.977), and the intraclass correlation coefficient exceeded 0.90 for all cases. The correlation coefficient for the number of medications was 0.955 (P < 0.001). Weak significant correlations were observed with age and length of stay. The MRCI-K group with ADR reports scored higher (mean, 31.8) than the group without ADR reports (mean, 27.3). The expert panel's ranking had a stronger correlation with the MRCI ranking than the medication number ranking. MRCI-K has similar reliability and validity as MRCI and is useful for analyzing therapeutic regimens with potential applications in both practice and research in Korea

DataSheet1_Population pharmacokinetics of everolimus in patients with seizures associated with focal cortical dysplasia.PDF

Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type Ⅱ (FCD Ⅱ) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed.Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States).Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5–15 ng/mL.Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg.</p