In vitro-in vivo correlation of hepatobiliary drug clearance in humans

Clin Pharmacol Ther. 2007 Mar;81(3):406-13. doi: 10.1038/sj.clpt.6100059. Epub 2007 Jan 18.


The biliary clearance (Cl(biliary)) of three compounds was estimated using sandwich-cultured human hepatocytes (SCHH) and compared with Cl(biliary) values measured in vivo. Tc-99m sestamibi (MIBI) Cl(biliary) was determined in seven healthy volunteers using an oroenteric catheter to aspirate duodenal secretions, and gamma scintigraphy to determine gallbladder contraction; this technique was used previously to determine Tc-99m mebrofenin (MEB) and piperacillin (PIP) in vivo Cl(biliary). In vitro Cl(biliary) of MEB, MIBI, and PIP was quantified in SCHH as the ratio of mass excreted into bile canaliculi and area under the blood concentration-time curve (AUC) in medium. MIBI Cl(biliary) in vivo was 5.5+/-1.2 mL/min/kg (mean+/-SD). The rank order of Cl(biliary) predicted from SCHH corresponded well with the in vivo Cl(biliary) values in mL/min/kg for MEB (7.44 vs 16.1), MIBI (1.20 vs 5.51), and PIP (0.028 vs 0.032). In conclusion, the methods developed allowed for reproducible quantification of Cl(biliary) of drugs in healthy humans and prediction of Cl(biliary) from in vitro data.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Bile / metabolism*
  • Blood Pressure / drug effects
  • Cell Separation
  • Cells, Cultured
  • Female
  • Forecasting
  • Gallbladder Emptying / physiology
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism*
  • Living Donors
  • Male
  • Microscopy, Phase-Contrast
  • Middle Aged
  • Pharmaceutical Preparations / metabolism*
  • Radiopharmaceuticals / pharmacokinetics
  • Taurocholic Acid / metabolism
  • Technetium Tc 99m Sestamibi / pharmacokinetics
  • Tissue Donors


  • Pharmaceutical Preparations
  • Radiopharmaceuticals
  • Taurocholic Acid
  • Technetium Tc 99m Sestamibi