Simultaneous modelling of flosequinan and its metabolite
| Autor: | I. D. Hind, Byron Jones, W. D. Byrom, James K. Lindsey, Jixian Wang |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Time Factors Adolescent Metabolic Clearance Rate Vasodilator Agents Metabolite Administration Oral Pharmacology Placebo Models Biological law.invention chemistry.chemical_compound Double-Blind Method Pharmacokinetics Oral administration law Internal medicine medicine Humans Tissue Distribution Pharmacology (medical) Dosing Flosequinan Cross-Over Studies Clinical pharmacology Dose-Response Relationship Drug Alanine Transaminase General Medicine Middle Aged chemistry Area Under Curve Data Interpretation Statistical Censoring (clinical trials) Quinolines Female medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 55:827-836 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s002280050704 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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