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2000
Volume 21, Issue 10
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Background: In vitro-in vivo extrapolation (IVIVE) of hepatic drug clearance () involves the scaling of hepatic intrinsic clearance () by functional liver size, which is approximated by total liver volume () as per the convention. However, in most overweight and obese patients, includes abnormal liver fat, which is not thought to contribute to drug elimination, thus overestimating drug . Therefore, lean liver volume () might be a more appropriate scaler of . Objective: The objective of this work was to assess the application of in extrapolation in overweight and obese patients (BMI >25 kg/m2) using a model drug antipyrine. Methods: Recently, a model to predict from patient sex, weight, and height was developed and evaluated. In order to assess the model’s use in IVIVE, a correlation-based analysis was conducted using antipyrine as an example drug. Results: In the overweight group (BMI >25 kg/m2), could describe 36% of the variation in antipyrine (2 = 0.36), which was >2-fold higher than that was explained by (2 = 0.17). In the normal-weight group (BMI ≤25 kg/m2), the coefficients of determination were 58% (2 = 0.58) and 43% (2= 0.43) for and , respectively. ; Conclusion: The analysis indicates that is potentially a more appropriate descriptor of functional liver size than , particularly in overweight individuals. Therefore, has a potential application in IVIVE of in obesity.

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/content/journals/cdm/10.2174/1389200221666200515105800
2020-08-01
2025-05-22
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