Expert Review of Clinical Pharmacology最新文献

Background: Variability exists in sertraline pharmacokinetic parameters in individuals, especially obvious in adolescents. We aimed to establish an individualized dosing model of sertraline for adolescents with depression based on artificial intelligence (AI) techniques.

Methods: Data were collected from 258 adolescent patients treated at the First Hospital of Hebei Medical University between December 2019 to July 2022. Nine different algorithms were used for modeling to compare the prediction abilities on sertraline daily dose, including XGBoost, LGBM, CatBoost, GBDT, SVM, ANN, TabNet, KNN, and DT. Performance of four dose subgroups (50 mg, 100 mg, 150 mg, and 200 mg) were analyzed.

Results: CatBoost was chosen to establish the individualized medication model with the best performance. Six important variables were found to be correlated with sertraline dose, including plasma concentration, PLT, MPV, GL, A/G, and LDH. The ROC curve and confusion matrix exhibited the good prediction performance of CatBoost model in four dose subgroups (the AUC of 50 mg, 100 mg, 150 mg, and 200 mg were 0.93, 0.81, 0.93, and 0.93, respectively).

Conclusion: The AI-based dose prediction model of sertraline in adolescents with depression had a good prediction ability, which provides guidance for clinicians to propose the optimal medication regimen.

Background: This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting β₂-agonists (ICS/LABA) in bronchiectasis.

Research design and methods: A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography.

Results: Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81-1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84-1.33) for acute exacerbation, and 1.06 (95% CI 0.66-1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43-0.81; BUD/FOR HR 0.68, 95% CI 0.50-0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26-0.86) and all-cause hospitalization (HR 0.55, 95% 0.37-0.80) compared to FLU/SAL.

Conclusion: Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.

Background: Metformin has the potential for treating numerous diseases, but there are still many unrecognized and unreported adverse events (AEs).

Methods: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2022 for disproportionality analysis to assess the association between metformin and related adverse events.

Results: In this study 10,500,295 case reports were collected from the FAERS database, of which 56,674 adverse events related to metformin were reported. A total of 643 preferred terms (PTs) and 27 system organ classes (SOCs) that were significant disproportionality conforming to the four algorithms simultaneously were included. The SOCs included metabolic and nutritional disorders (p = 0.00E + 00), gastrointestinal disorders (p = 0.00E + 00) and others. PT levels were screened for adverse drug reaction (ADR) signals such as acute pancreatitis (p = 0.00E + 00), melas syndrome, pemphigoid (p = 0.00E + 00), skin eruption (p = 0.00E + 00) and drug exposure during pregnancy (p = 0.00E + 00).

Conclusion: Most of our results were consistent with the specification, but some new signals of adverse reactions such as acute pancreatitis were not included. Therefore, further studies are needed to validate unlabeled adverse reactions and provide important support for clinical monitoring and risk identification of metformin.