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In Vitro – In Vivo Correlation of Hepatobiliary Drug Clearance in Humans
Author(s) -
Ghibellini G,
Vasist L S,
Leslie E M,
Heizer W D,
Kowalsky R J,
Calvo B F,
Brouwer K L R
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100059
Subject(s) - in vivo , in vitro , chemistry , gallbladder , pharmacokinetics , scintigraphy , pharmacology , medicine , nuclear medicine , biology , biochemistry , microbiology and biotechnology
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. Clinical Pharmacology & Therapeutics (2007) 81 , 406–413. doi: 10.1038/sj.clpt.6100059 ; published online 18 January 2007