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Hepatic clearance of drugs. III. Additional experimental evidence supporting the “wellstirred” model, using metabolite (MEGX) generated from lidocaine under varying hepatic blood flow rates and linear conditions in the perfused rat liverin situ preparation

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Abstract

The disposition of monoethylglycine xylidide (MEGX), a metabolite of lidocaine, was studied in the perfused rat liver in situpreparation in an attempt to further discriminate between two models of hepatic drug clearance. In the “well-stirred” model, the liver is regarded as a well-stirred compartment with the emergent drug concentration in equilibrium with that in the liver. In the “parallel tube” model, the liver is viewed as a series of indentical paralllel units with enzymes distributed evenly around the units. Using a single-passage perfusate system, we found in a previous study that the extraction ratio of lidocaine was maximal and constant (0.997) below 7 mg/liter. The steady-state output MEGX concentration appearing in the emergent blood upon a constant and low-input concentration of lidocaine (4 mg/liter) was determined under varying hepatic blood flow rates (10–16 ml/min per liver). The data suggest that operationally the “well-stirred” model adequately describes the appearance of MEGX from lidocaine.

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Supported in part by National Institutes of Health Grant GM 16496 and the Patent Fund, Graduate Division, University of California, San Francisco.

Abstracted in part from a dissertation by K. Sandy Pang to the Graduate Division, University of California, San Francisco, California, in partial fulfillment of the Doctor of Philosophy degree requirement.

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Pang, K.S., Rowland, M. Hepatic clearance of drugs. III. Additional experimental evidence supporting the “wellstirred” model, using metabolite (MEGX) generated from lidocaine under varying hepatic blood flow rates and linear conditions in the perfused rat liverin situ preparation. Journal of Pharmacokinetics and Biopharmaceutics 5, 681–699 (1977). https://doi.org/10.1007/BF01059690

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  • DOI: https://doi.org/10.1007/BF01059690

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