This study aimed to develop a population pharmacokinetic model using full pharmacokinetic (PK) profiles of isoniazid (INH) taking into account demographic and genetic covariates and to develop Bayesian estimators for predicting INH area under the curve (AUC) in Tunisian tuberculosis patients. The INH concentrations in the building data set were fitted using a one- to three-compartment model. The impact of the different covariates was assessed on the PK parameters of the best model. The best limited sampling strategy (LSS) for estimating the INH AUC was selected by comparing the predicted values to an independent data set. INH PK was best described using a three-compartment model with lag-time absorption. The different studied covariates did not have any impact on the PK parameters of the building model. The Bayesian estimation using one-point concentrations gave the lowest values of prediction errors for the C LSS model. This model could be sufficient in routine activity for INH monitoring in this population.
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http://dx.doi.org/10.1038/s41397-021-00223-x | DOI Listing |
J Med Chem
December 2024
Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.
View Article and Find Full Text PDFDrug Des Devel Ther
December 2024
Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.
Background And Objective: Vancomycin is commonly prescribed in treatment of methicillin-resistant Staphylococcus aureus infections. While, vancomycins' pharmacokinetic vary among older patients, there is a paucity of data regarding specific characteristics influencing pharmacokinetics in Saudi adult patients. This study aims to establish a population-pharmacokinetic (Pop-PK) model for vancomycin in patients admitted to medical wards, with the focus on identification of patient characteristics influencing vancomycin trough concentrations.
View Article and Find Full Text PDFClin Pharmacokinet
December 2024
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, P. O. Box 30001, 9700 RB, Groningen, The Netherlands.
Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.
View Article and Find Full Text PDFClin Ther
December 2024
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China. Electronic address:
Purpose: Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase that plays a critical role in human cancers. The current clinical trial aimed to assess the pharmacokinetic properties, safety, and tolerability of ipatasertib administered to Chinese patients with locally advanced or metastatic solid tumors.
Methods: A Phase I, single-arm, open-label study was performed in Chinese patients with locally advanced or metastatic solid tumors for whom standard therapy either does not exist or has proven ineffective.
J Pharm Biomed Anal
December 2024
Service of Clinical Pharmacology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Levosimendan is a positive inotrope and vasodilator used in patients with acute and chronic decompensated heart failure. It is metabolized into OR-1855 (inactive metabolite), which is further acetylated into OR-1896 (active metabolite having a prolonged half-life, hence a sustained effect). Levosimendan represents a valuable alternative to traditional inotropes with broad clinical applications in critically ill patients with cardiogenic shock, advanced heart failure and post-cardiac surgery.
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