Ian Morris

The University of York, York, England, United Kingdom

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Publications (1)5.05 Total impact

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    ABSTRACT: The aim of this crossover human male volunteer study was to investigate the utility of microdosing in the investigation of drug-drug interactions. A mixture of midazolam, tolbutamide, caffeine and fexofenadine were administered as a microdose (25 μg each) before and after administration of a combined pharmacological dose of ketoconazole (400 mg) and fluvoxamine (100 mg) to inhibit P-glycoprotein and metabolism by cytochrome P450 (CYP) 1A2, CYP3A4 and CYP2C9. When administered alone, pharmacokinetics for all four microdosed compounds scaled well with those reported for therapeutic doses and with previously performed microdose studies. The pharmacokinetics of each compound administered as a microdose were significantly altered after the administration of ketoconazole and fluvoxamine, showing statistically significant (p < 0.01) 12.8-, 8.1- and 3.2-fold increases in the area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) for midazolam, caffeine and fexofenadine, respectively. A 1.8-fold increase (not statistically significant) in AUC(∞) was observed for tolbutamide. The changes in pharmacokinetics mediated by ketoconazole and fluvoxamine were quantitatively consistent with previously reported, non-microdose, drug-drug interaction data from studies including the same compounds. The initial data reported here demonstrate the utility of microdosing to investigate the risk of development drugs being victims of drug-drug interactions.
    No preview · Article · Feb 2012 · Clinical Pharmacokinetics

Publication Stats

17 Citations
5.05 Total Impact Points

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  • 2012
    • The University of York
      • Hull York Medical School
      York, England, United Kingdom