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Microsomal protein per gram of liver (MPPGL) in paediatric biliary atresia patients

Lies De Bock1, Koen Boussery, Ruth De Bruyne

  • 1Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium.

Biopharmaceutics & Drug Disposition
|March 20, 2014
PubMed

Insights

Microsomal protein per gram of liver (MPPGL) was lower in pediatric biliary atresia patients than expected. This finding suggests reduced microsomal protein in livers affected by this disease, impacting drug metabolism studies.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Hepatology
  • Pediatric Gastroenterology

Background:

  • Microsomal protein per gram of liver (MPPGL) is crucial for in vitro-in vivo extrapolation of metabolic data.
  • Age and liver disease are known factors influencing MPPGL.
  • Biliary atresia is a pediatric liver disease affecting liver function.

Purpose of the Study:

  • To determine the MPPGL in pediatric patients with biliary atresia.
  • To compare observed MPPGL values with age-expected values.
  • To investigate potential differences in MPPGL across liver zones.

Main Methods:

  • MPPGL determination in liver microsomes from four biliary atresia patients (0.6-1.6 years old).
  • NADPH-cytochrome reductase activity used to calculate recovery factor due to bilirubin interference.
  • Comparison of measured MPPGL with established age-dependent reference values.

Main Results:

  • A mean MPPGL of 18.73 (± 2.82) mg/g was observed in biliary atresia patients.
  • This value is significantly lower than the age-predicted MPPGL of 26.60 (± 0.40) mg/g.
  • No significant differences in MPPGL were detected between different liver zones.

Conclusions:

  • Pediatric patients with biliary atresia exhibit a reduced amount of microsomal protein in their livers.
  • The lower MPPGL in these patients may affect the accuracy of in vitro-in vivo extrapolation for drug metabolism studies.
  • Further research is needed to understand the implications of reduced MPPGL in pediatric liver diseases.
Keywords:
biliary atresiacytochrome P450in vitro-in vivo extrapolation (IVIVE)microsomal protein per gram liver (MPPGL)

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