Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/5605
Title: | Simultaneous modelling of flosequinan and its metabolite | Authors: | LINDSEY, James WANG, Jihui Jones, Bradley Byrom, W.D. Hind, I.D. |
Issue Date: | 2000 | Publisher: | Springer | Source: | European journal of clinical pharmacology, 55. p. 827-836 | Abstract: | 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 96h after dosing. Setting: Clinical pharmacology unit in a pharmaceutical company. Participants: Eighty 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 metabollite 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. | Document URI: | http://hdl.handle.net/1942/5605 | ISI #: | 000086651300009 | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Show full item record
WEB OF SCIENCETM
Citations
4
checked on Sep 26, 2024
Page view(s)
170
checked on Nov 7, 2023
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.