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dc.contributor.authorSchellens, J. H. M.en
dc.contributor.authorDombernowsky, P.en
dc.contributor.authorCassidy, J.en
dc.contributor.authorEpelbaum, R.en
dc.contributor.authorDirix, L.en
dc.contributor.authorCox, E. H.en
dc.contributor.authorWanders, J.en
dc.contributor.authorCalabresi, F.en
dc.contributor.authorParidaens, R.en
dc.contributor.authorMonfardini, S.en
dc.contributor.authorWolff, J.en
dc.contributor.authorLoos, W. J.en
dc.contributor.authorVerweij, J.en
dc.contributor.authorPavlidis, Nicholasen
dc.contributor.authorHanauske, A. R.en
dc.creatorSchellens, J. H. M.en
dc.creatorDombernowsky, P.en
dc.creatorCassidy, J.en
dc.creatorEpelbaum, R.en
dc.creatorDirix, L.en
dc.creatorCox, E. H.en
dc.creatorWanders, J.en
dc.creatorCalabresi, F.en
dc.creatorParidaens, R.en
dc.creatorMonfardini, S.en
dc.creatorWolff, J.en
dc.creatorLoos, W. J.en
dc.creatorVerweij, J.en
dc.creatorPavlidis, Nicholasen
dc.creatorHanauske, A. R.en
dc.date.accessioned2018-06-22T09:53:09Z
dc.date.available2018-06-22T09:53:09Z
dc.date.issued2001
dc.identifier.urihttps://gnosis.library.ucy.ac.cy/handle/7/41688
dc.description.abstractPopulation 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.isoengen
dc.sourceAnti-Cancer Drugsen
dc.subjectArticleen
dc.subjectAntineoplastic agentsen
dc.subjectCancer chemotherapyen
dc.subjectHumanen
dc.subjectNeoplasmsen
dc.subject80 and overen
dc.subjectAgeden
dc.subjectHumansen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectControlled studyen
dc.subjectFemaleen
dc.subjectMajor clinical studyen
dc.subjectMiddle ageden
dc.subjectAlgorithmen
dc.subjectDrug responseen
dc.subjectPriority journalen
dc.subjectClinical trialen
dc.subjectControlled clinical trialen
dc.subjectDrug safetyen
dc.subjectPhase 2 clinical trialen
dc.subjectProspective studiesen
dc.subjectArea under the curveen
dc.subjectProspective studyen
dc.subjectDrug exposureen
dc.subjectMaleen
dc.subjectUnclassified drugen
dc.subjectCytotoxic agenten
dc.subjectDrug clearanceen
dc.subjectPharmacokineticsen
dc.subjectPhase 1 clinical trialen
dc.subjectAlkylating agenten
dc.subjectArea under curveen
dc.subjectPhase iien
dc.subject5 (1 aziridinyl) 3 hydroxymethyl 2 (3 hydroxy 1 propenyl) 1 methyl 4en
dc.subject7 indoledioneen
dc.subjectAziridinesen
dc.subjectEo9en
dc.subjectIndolequinonesen
dc.subjectIndolesen
dc.subjectPharmacodynamicsen
dc.subjectBayesian algorithmen
dc.subjectIndoloquinoneen
dc.subjectMetabolic clearance rateen
dc.subjectPopulation analysisen
dc.subjectPopulation dynamicsen
dc.subjectQuinone derivativeen
dc.subjectSampling studiesen
dc.titlePopulation pharmacokinetics and dynamics in phase II studies of the novel bioreductive alkylating cytotoxic indoloquinone EO9en
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1097/00001813-200108000-00004
dc.description.volume12
dc.description.issue7
dc.description.startingpage583
dc.description.endingpage590
dc.author.facultyΙατρική Σχολή / Medical School
dc.type.uhtypeArticleen


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