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PI‐48
Author(s) -
Ghibellini G.,
Vasist L. S.,
Heizer W. D.,
Kowalsky R. J.,
Brouwer K. L.
Publication year - 2006
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 - 10.1016/j.clpt.2005.12.069
Subject(s) - excretion , medicine , gastroenterology , endocrinology , cardiology , nuclear medicine
BACKGROUND/AIMS Tc‐99m sestamibi (MIBI), a myocardial imaging agent, is a P‐gp, MRP1, Mrp2, and BCRP substrate. This study was designed to assess Tc‐99m MIBI biliary clearance in healthy volunteers utilizing a customized oroenteric tube and clinical protocol. METHODS This open‐label study was conducted at the UNC GCRC. Healthy volunteers (n=7) were administered a 5 μCi IV bolus of Tc‐99m MIBI (Cardiolite®, Bristol‐Myers Squibb). Blood, urine, and duodenal aspirates (via the oroenteric tube) were collected at designated intervals. Tc‐99m MIBI was quantified and pharmacokinetic parameters were calculated by noncompartmental analysis. Gallbladder ejection fraction (EF), determined by gamma scintigraphy, was used to correct the biliary clearance calculation. RESULTS Total systemic clearance of Tc‐99m MIBI was 17.1 ± 2.5 mL/min/kg; 4.7% to 21.6% of the dose was recovered in bile. Biliary clearance corrected for EF was 5.5 ± 1.2 mL/min/kg and accounted for 32.2% of total clearance; renal clearance accounted for 24.6 %. Imaging of the abdominal area allowed for visualization of Tc‐99m MIBI intestinal secretion. CONCLUSIONS This novel method is useful to quantify biliary clearance in healthy subjects. Correction for EF decreases intersubject variability. The complete collection of biliary secretions combined with data from abdominal images suggests that intestinal secretion is an additional clearing mechanism for this compound. Clinical Pharmacology & Therapeutics (2005) 79 , P19–P19; doi: 10.1016/j.clpt.2005.12.069