caa a22 4500 475818059 CHVBK 20180406123814.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s002280050704 doi (NATIONALLICENCE)springer-10.1007/s002280050704 Simultaneous modelling of flosequinan and its metabolite [Elektronische Daten] [J. K. Lindsey, J. Wang, B. Jones, W. D. Byrom, I. D. Hind] Design: A randomised, double-blind, prospective, placebo-controlled four-way study of the pharmacokinetics of single oral doses of flosequinan. We do not report the placebo data in this paper. Flosequinan was given at doses of 50, 100 and 150 mg, with a 2-week wash-out between periods. Blood samples were taken at a series of times up to 96 h after dosing. Setting: Clinical pharmacology unit in a pharmaceutical company. Participants: Eighteen healthy volunteers of both genders, aged from 18 years to 55 years. Main outcome measures: Plasma concentrations of flosequinan and of its metabolite, flosequinoxan. Results: We demonstrate that it is possible to model parent and metabolite concentration-time profiles simultaneously and, in doing so, to estimate the first-pass effect using data from an oral administration. In our modelling approach, we propose a reasonably wide class of statistical models, allowing for left censoring. Conclusions: A parent-metabolite model that ignores the first-pass results in misleading predictions in a case where significant first-pass metabolism occurs. Thus, in phase-I studies, the new approach described in this paper can provide additional knowledge that may be useful in future formal studies. Springer-Verlag Berlin Heidelberg, 2000 Key words First-pass metabolism nationallicence Gamma distribution nationallicence One-compartment model nationallicence Lindsey J. K. Department of Medical Statistics, De Montfort University, Leicester, LE1 9BH, UK e-mail: bj@dmu.ac.uk Tel.: +44-116-2577463; Fax: +44-116-2506114, GB aut Wang J. Department of Medical Statistics, De Montfort University, Leicester, LE1 9BH, UK e-mail: bj@dmu.ac.uk Tel.: +44-116-2577463; Fax: +44-116-2506114, GB aut Jones B. Department of Medical Statistics, De Montfort University, Leicester, LE1 9BH, UK e-mail: bj@dmu.ac.uk Tel.: +44-116-2577463; Fax: +44-116-2506114, GB aut Byrom W. D. BASF Pharma, Nottingham, UK, GB aut Hind I. D. BASF Pharma, Nottingham, UK, GB aut https://doi.org/10.1007/s002280050704 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050704 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lindsey J. K. Department of Medical Statistics, De Montfort University, Leicester, LE1 9BH, UK e-mail: bj@dmu.ac.uk Tel.: +44-116-2577463; Fax: +44-116-2506114, GB aut NATIONALLICENCE 700 1- Wang J. Department of Medical Statistics, De Montfort University, Leicester, LE1 9BH, UK e-mail: bj@dmu.ac.uk Tel.: +44-116-2577463; Fax: +44-116-2506114, GB aut NATIONALLICENCE 700 1- Jones B. Department of Medical Statistics, De Montfort University, Leicester, LE1 9BH, UK e-mail: bj@dmu.ac.uk Tel.: +44-116-2577463; Fax: +44-116-2506114, GB aut NATIONALLICENCE 700 1- Byrom W. D. BASF Pharma, Nottingham, UK, GB aut NATIONALLICENCE 700 1- Hind I. D. BASF Pharma, Nottingham, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer