Background: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF.
Materials And Methods: We compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (v, K, k) in muscle-located outside the radiation area-were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans.
Results: Several parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: v (0.65, 0.74, 0.58, 0.32), K (0.30, 0.21, 0.13, 0.06), k (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs.
Conclusion: Image-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area.
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http://dx.doi.org/10.1016/j.mri.2020.01.010 | DOI Listing |
J Magn Reson
January 2025
UC Berkeley - UCSF Graduate Program in Bioengineering, 1700 4th St, San Francisco, CA 94158, USA; Radiology and Biomedical Imaging, University of California, San Francisco, 1700 4th St, San Francisco, CA 94158, USA.
Fitting rate constants to Hyperpolarized [1-C]Pyruvate (HP C13) MRI data is a promising approach for quantifying metabolism in vivo. Current methods typically fit each voxel of the dataset using a least-squares objective. With these methods, each voxel is considered independently, and the spatial relationships are not considered during fitting.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
January 2025
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Everolimus presents significant dosing challenges due to between- and within-patient pharmacokinetic variabilities. This study aimed to develop and validate a model-informed precision dosing strategy for everolimus in liver transplant recipients. The dosing strategy was initially developed using retrospective data, employing nonlinear mixed-effects modeling.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
January 2025
BGL, BioGenomics Ltd, Maharashtra, India.
Insulin aspart, a rapid-acting analog, achieves faster subcutaneous absorption than regular insulin. This study aimed to demonstrate equivalence in the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of Recombinant Human Insulin Aspart from BioGenomics Limited (as test) and Novo-Nordisk (as reference) in healthy adult males. This was a double-blind, randomized, cross-over study, assessing PK and PD parameters under fasting conditions.
View Article and Find Full Text PDFClin Pharmacokinet
January 2025
Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
Background And Objective: Psilocybin is currently being extensively studied as a potential therapeutic agent for multiple psychiatric disorders. Here, a systematic literature review of all published pharmacokinetic data on the pharmacologically active metabolite of psilocybin, psilocin, is presented.
Methods: The review includes clinical studies that reported pharmacokinetic data and/or parameters after psilocybin administration in humans.
J Antimicrob Chemother
January 2025
URP 7328 Federation for Research into Innovative Explorations and Therapeutics in Utero, University of Paris-Cité, Paris, France.
Background: In cases of maternal primary infection with cytomegalovirus (CMV-MPI) maternal treatment with oral valaciclovir 8 g/day has been shown to reduce the risk of fetal infection. The pharmacological profile of this high dosage during pregnancy is not yet known.
Objectives: To quantify maternal-fetal exposure to valaciclovir 8 g/day in a population pharmacokinetic (popPK) study.
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