Population pharmacokinetics and dynamics in phase II studies of the novel bioreductive alkylating cytotoxic indoloquinone EO9
dc.contributor.author | Schellens, J. H. M. | en |
dc.contributor.author | Dombernowsky, P. | en |
dc.contributor.author | Cassidy, J. | en |
dc.contributor.author | Epelbaum, R. | en |
dc.contributor.author | Dirix, L. | en |
dc.contributor.author | Cox, E. H. | en |
dc.contributor.author | Wanders, J. | en |
dc.contributor.author | Calabresi, F. | en |
dc.contributor.author | Paridaens, R. | en |
dc.contributor.author | Monfardini, S. | en |
dc.contributor.author | Wolff, J. | en |
dc.contributor.author | Loos, W. J. | en |
dc.contributor.author | Verweij, J. | en |
dc.contributor.author | Pavlidis, Nicholas | en |
dc.contributor.author | Hanauske, A. R. | en |
dc.creator | Schellens, J. H. M. | en |
dc.creator | Dombernowsky, P. | en |
dc.creator | Cassidy, J. | en |
dc.creator | Epelbaum, R. | en |
dc.creator | Dirix, L. | en |
dc.creator | Cox, E. H. | en |
dc.creator | Wanders, J. | en |
dc.creator | Calabresi, F. | en |
dc.creator | Paridaens, R. | en |
dc.creator | Monfardini, S. | en |
dc.creator | Wolff, J. | en |
dc.creator | Loos, W. J. | en |
dc.creator | Verweij, J. | en |
dc.creator | Pavlidis, Nicholas | en |
dc.creator | Hanauske, A. R. | en |
dc.date.accessioned | 2018-06-22T09:53:09Z | |
dc.date.available | 2018-06-22T09:53:09Z | |
dc.date.issued | 2001 | |
dc.identifier.uri | https://gnosis.library.ucy.ac.cy/handle/7/41688 | |
dc.description.abstract | Population pharmacokinetic-dynamic analysis was prospectively integrated in the clinical phase II programme of EO9 to determine the population pharmacokinetic profile in a larger population of patients, to estimate individual patient pharmacokinetic parameters, and to investigate relationships between drug exposure and clinical outcome. A sparse sampling method was developed, which involved three sampling times, and was implemented during course 1. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) of EO9 and area under the curve (AUC). In total, samples were collected of 85 (65%) of the patients. Pharmacokinetic evaluation was successful in 61 (72%) of the sampled patients. CL of EO9 showed substantial variability (median 5.08 l/min; range 2.67-6.42) and was of the same magnitude as in the phase I study where full pharmacokinetic profiles were used. No significant relationships were noticed between exposure parameters and safety, but overall limited toxicity was observed. No tumor responses were documented. Prospective implementation of large-scale population pharmacokinetic-dynamic analysis is feasible and may generate important findings, in particular when tumor responses and relevant toxicity are observed. © 2001 Lippincott Williams & Wilkins. | en |
dc.language.iso | eng | en |
dc.source | Anti-Cancer Drugs | en |
dc.subject | Article | en |
dc.subject | Antineoplastic agents | en |
dc.subject | Cancer chemotherapy | en |
dc.subject | Human | en |
dc.subject | Neoplasms | en |
dc.subject | 80 and over | en |
dc.subject | Aged | en |
dc.subject | Humans | en |
dc.subject | Adult | en |
dc.subject | Aged | en |
dc.subject | Controlled study | en |
dc.subject | Female | en |
dc.subject | Major clinical study | en |
dc.subject | Middle aged | en |
dc.subject | Algorithm | en |
dc.subject | Drug response | en |
dc.subject | Priority journal | en |
dc.subject | Clinical trial | en |
dc.subject | Controlled clinical trial | en |
dc.subject | Drug safety | en |
dc.subject | Phase 2 clinical trial | en |
dc.subject | Prospective studies | en |
dc.subject | Area under the curve | en |
dc.subject | Prospective study | en |
dc.subject | Drug exposure | en |
dc.subject | Male | en |
dc.subject | Unclassified drug | en |
dc.subject | Cytotoxic agent | en |
dc.subject | Drug clearance | en |
dc.subject | Pharmacokinetics | en |
dc.subject | Phase 1 clinical trial | en |
dc.subject | Alkylating agent | en |
dc.subject | Area under curve | en |
dc.subject | Phase ii | en |
dc.subject | 5 (1 aziridinyl) 3 hydroxymethyl 2 (3 hydroxy 1 propenyl) 1 methyl 4 | en |
dc.subject | 7 indoledione | en |
dc.subject | Aziridines | en |
dc.subject | Eo9 | en |
dc.subject | Indolequinones | en |
dc.subject | Indoles | en |
dc.subject | Pharmacodynamics | en |
dc.subject | Bayesian algorithm | en |
dc.subject | Indoloquinone | en |
dc.subject | Metabolic clearance rate | en |
dc.subject | Population analysis | en |
dc.subject | Population dynamics | en |
dc.subject | Quinone derivative | en |
dc.subject | Sampling studies | en |
dc.title | Population pharmacokinetics and dynamics in phase II studies of the novel bioreductive alkylating cytotoxic indoloquinone EO9 | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1097/00001813-200108000-00004 | |
dc.description.volume | 12 | |
dc.description.issue | 7 | |
dc.description.startingpage | 583 | |
dc.description.endingpage | 590 | |
dc.author.faculty | Ιατρική Σχολή / Medical School | |
dc.author.department | Ιατρική Σχολή / Medical School | |
dc.type.uhtype | Article | en |
dc.contributor.orcid | Pavlidis, Nicholas [0000-0002-2195-9961] | |
dc.gnosis.orcid | 0000-0002-2195-9961 |
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