Mixed effects modeling of radiotherapy in combination with immune checkpoint blockade or inhibitors of the DNA damage response pathway

Autor: David Hodson, Hitesh Mistry, Sofia Guzzetti, Michael Davies, Anna Staniszewska, Paul Farrington, Elaine Cadogan, James Yates, Leon Aarons, Kayode Ogungbenro

Publikováno v: CPT: Pharmacometrics & Systems Pharmacology, Vol 12, Iss 11, Pp 1640-1652 (2023)

Abstract Dosage optimization to maximize efficacy and minimize toxicity is a potential issue when administering radiotherapy (RT) in combination with immune checkpoint blockade (ICB) or inhibitors of the DNA Damage Response Pathway (DDRi) in the clin

Externí odkaz: https://doaj.org/article/6a94e1fb15584edda03e4b6cd2be34da

A 'middle‐out approach' for the prediction of human drug disposition from preclinical data using simplified physiologically based pharmacokinetic (PBPK) models

Autor: Estelle Yau, Michael Gertz, Kayode Ogungbenro, Leon Aarons, Andrés Olivares‐Morales

Publikováno v: CPT: Pharmacometrics & Systems Pharmacology, Vol 12, Iss 3, Pp 346-359 (2023)

Abstract Simplified physiologically based pharmacokinetic (PBPK) models using estimated tissue‐to‐unbound plasma partition coefficients (Kpus) were previously investigated by fitting them to in vivo pharmacokinetic (PK) data. After optimization w

Externí odkaz: https://doaj.org/article/ae947b9e7b6946dda689634831c73464

Evaluation of area under the concentration curve adjusted by the terminal‐phase as a metric to reduce the impact of variability in bioequivalence testing

Autor: Chao Chen, Kayode Ogungbenro, Leon Aarons, Shuying Y Yang, Adam J Lucas

Publikováno v: British Journal of Clinical Pharmacology. 88:619-627

Aim To quantify the utility of a terminal-phase adjusted area under the concentration curve method in increasing the probability of a correct and conclusive outcome of a bioequivalence (BE) trial for highly variable drugs when clearance (CL) varies m

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::547f9c144d5b0fb0f48a472a8b011f18
https://doi.org/10.1111/bcp.14986

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4: Prediction accuracy and software comparisons with improved data and modelling strategies

Autor: Alex Mattinson, David Lindley, Helena Engman, Manthena V.S. Varma, Anh-Thu Nguyen-Trung, Binfeng Xia, Xavier Pepin, Linette Ruston, Wei Zhu, Bill van Osdol, Celine Ollier, David Good, Jonathan Brown, Laurent Boulu, Talia Flanagan, Olivier Nicolas, Staffan Berg, Shanoo Budhdeo, Aarti Patel, Jan Bevernage, Handan He, Sweta Modi, Richard Barker, Claire Jackson, Christer Tannergren, Xiojun Ren, Stephane Beilles, J. Matthew Wood, Johanna Laru, Pierre Daublain, Sara Carlert, Louis Henrion, Jean-Flaubert Nguefack, Gunilla Hanisch, Eva Karlsson, Wen Lin, Shruthi Vaidhyanathan, Robert Carr, Fan Wu, Jin Zhang, Amais Ahmad, James M. Mullin, Sari Pappinen, Andrea Moir, Ke Szeto, Christine Xu, Claire Patterson, David B. Turner, Guillaume Louit, Yuya Wang, Tycho Heimbach, Richard Lloyd, Frans Franek, Masoud Jamei, Christophe Tistaert, Bertil Abrahamsson, Kerstin Julia Schäfer, Leon Aarons, Shriram M. Pathak, Adam S. Darwich, Suet Wong, Dónal Murphy, Amin Rostami-Hodjegan, Timo Korjamo, Helena Thörn, Kartrin Schmid, Michael B. Bolger, Johanna Tuunainen, Mai Anh Nguyen

Publikováno v: European Journal of Pharmaceutics and Biopharmaceutics. 156:50-63

Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinet

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bca05a74d852f38ad03c52e9e4fba40
https://doi.org/10.1016/j.ejpb.2020.08.006

Model-based drug-drug interaction extrapolation strategy from adults to children – risdiplam in pediatric patients with spinal muscular atrophy

Autor: Leon Aarons, Heidemarie Kletzl, Yumi Cleary, Michael Gertz, Andreas Günther, Katja Heinig, Aleksandra Galetin, Kayode Ogungbenro, Paul Grimsey

Publikováno v: Fukushima (Cleary), Y, Gertz, M, Grimsey, P, Günther, A, Heinig, K, Ogungbenro, K, Aarons, L, Galetin, A & Kletzl, H 2021, ' Model-based drug-drug interaction extrapolation strategy from adults to children – risdiplam in pediatric patients with spinal muscular atrophy ', Clinical Pharmacology & Therapeutics . https://doi.org/10.1002/cpt.2384

Risdiplam (Evrysdi) improves motor neuron function in patients with spinal muscular atrophy (SMA) and has been approved for the treatment of patients ≥2 months old. Risdiplam exhibits time-dependent inhibition of cytochrome P450 (CYP) 3A in vitro.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60d9913e9af5e9910daa01792db02396
https://www.research.manchester.ac.uk/portal/en/publications/modelbased-drugdrug-interaction-extrapolation-strategy-from-adults-to-children--risdiplam-in-pediatric-patients-with-spinal-muscular-atrophy(c85742c4-c14d-419d-9311-c599b740e7f5).html