Model-informed precision dosing is being increasingly used to improve therapeutic drug monitoring. To meet this need, several tools have been developed, but open-source software remains uncommon. Posologyr is a free and open-source R package developed to enable Bayesian individual parameter estimation and dose individualization. Before using it for clinical practice, performance validation is mandatory. The estimation functions implemented in posologyr were benchmarked against reference software products on a wide variety of models and pharmacokinetic profiles: 35 population pharmacokinetic models, with 4.000 simulated subjects by model. Maximum A Posteriori (MAP) estimates were compared to NONMEM post hoc estimates, and full posterior distributions were compared to Monolix conditional distribution estimates. The performance of MAP estimation was excellent in 98.7% of the cases. Considering the full posterior distributions of individual parameters, the bias on dosage adjustment proposals was acceptable in 97% of cases with a median bias of 0.65%. These results confirmed the ability of posologyr to serve as a basis for the development of future Bayesian dose individualization tools.
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http://dx.doi.org/10.3390/pharmaceutics14020442 | DOI Listing |
Pharmacotherapy
January 2025
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Background: Lamotrigine clearance can change drastically in pregnant women with epilepsy (PWWE) making it difficult to assess the need for dosing adjustments. Our objective was to characterize lamotrigine pharmacokinetics in PWWE during pregnancy and postpartum along with a control group of nonpregnant women with epilepsy (NPWWE).
Methods: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study was a prospective, observational, 20 site, cohort study conducted in the United States (December 2012 and February 2016).
IBRO Neurosci Rep
June 2025
Department of Human Anatomy and Medical Physiology, Faculty of Health Sciences, University of Nairobi, P.O. Box 30197- 00100, Nairobi, Kenya.
Khat ( Forsk), the natural source of cathinone and other psychoactive agents, is chewed by millions of persons in eastern Africa and the Arabian Peninsula for its psychostimulant effect. Using the conditioned place preference paradigm, this study tested fresh khat extract for place preference induction, extinction, and reinstatement. Female mice treated with 100 and 250 mg/kg of khat extract showed conditioned place preference, which was extinguished following a 16-day khat-free period.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Hospital, Kobe, Japan.
Metyrapone is commonly used in the initial management of Cushing's syndrome to reduce hypercortisolemia, but its optimal dosage and timing can vary significantly between patients. Currently, there are limited guidelines on adjustment methods for its administration to individual needs. This study aimed to evaluate responsiveness of each patient to metyrapone and identify the patient characteristics associated with the indices of cortisol responsiveness following a low-dose metyrapone.
View Article and Find Full Text PDFEClinicalMedicine
August 2024
Division of Cancer Prevention and Population Sciences, Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background: Lung cancer screening recommendations employ annual frequency for eligible individuals, despite evidence that it may not be universally optimal. The impact of imposing a structure on the screening frequency remains unknown. The ENGAGE framework, a validated framework that offers fully dynamic, analytically optimal, personalised lung cancer screening recommendations, could be used to assess the impact of screening structure on the effectiveness and efficiency of lung cancer screening.
View Article and Find Full Text PDFApolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Individuals with one copy of APOE4 exhibit greater amyloid-beta (Aβ) deposition compared to noncarriers, an effect that is even more pronounced in APOE4 homozygotes. Interestingly, APOE4 carriers not only show more AD pathology but also experience more rapid cognitive decline, particularly in episodic memory.
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