Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 81, Issue 3, Pages 406-413Publisher
WILEY
DOI: 10.1038/sj.clpt.6100059
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Funding
- NCRR NIH HHS [RR00046] Funding Source: Medline
- NIGMS NIH HHS [R01 GM041935, R01 GM41935] Funding Source: Medline
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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.
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