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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Intraperitoneal and intraportal administration of droloxifene to the Sprague-Dawley rat: assessing the first-pass effect.

1. Employing droloxifene as a probe substrate, we have compared the use of intraperitoneal injection and intraportal infusion, where the rate and duration of intraportal drug administration were designed to approximate those observed after oral drug delivery, as methods of discriminating between high first-pass hepatic extraction and poor oral absorption. 2. Intraperitoneal injection of droloxifene (1 mg/kg) yielded an AUC0-omega approximately twice that observed following intraportal infusion or oral delivery of equal doses. 3. Our findings suggest that hepatic first-pass metabolism may have been saturated following intraperitoneal drug administration due to the rapid rate of absorption and the corresponding high drug concentrations achieved. 4. Application of a model in which intraportal drug infusion rates are designed to mimic the oral absorption rate appears warranted under such circumstances.[1]

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