Indocyanine green pharmacokinetics in the rabbit
Canadian Journal of Physiology and Pharmacology
|September 1, 1984
Summary
Indocyanine green (ICG) disposition in rabbits is dose-dependent, with higher doses showing reduced clearance and potential toxicity. A novel three-compartment model explains these findings, highlighting saturable liver uptake.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Toxicology
Background:
- Indocyanine green (ICG) is a vital diagnostic dye.
- Accurate quantification of ICG is crucial for clinical applications.
- Understanding ICG disposition and potential toxicity is essential.
Purpose of the Study:
- To investigate the pharmacokinetics of indocyanine green (ICG) in rabbits.
- To compare high-pressure liquid chromatography (HPLC) with spectrophotometry (SPEC) for ICG analysis.
- To elucidate the dose-dependent disposition and elimination of ICG.
Main Methods:
- Latin square design with nine male New Zealand white rabbits.
- Intravenous administration of ICG at 2.5, 12.5, and 25 mg/kg.
- Plasma and biliary ICG levels measured using HPLC and SPEC assays.
Main Results:
- HPLC revealed an unidentified ICG metabolite, while SPEC showed ambiguous results.
- ICG clearance was dose-dependent, decreasing with higher doses (17.09 to 2.27 mL x min-1 x kg-1).
- A three-compartment model with saturable liver uptake (Vmax = 0.93 mg x kg-1 x min-1) explained ICG disposition.
Conclusions:
- The spectrophotometric method for ICG analysis is less reliable than HPLC.
- ICG exhibits dose-dependent pharmacokinetics and potential cumulative toxicity in rabbits.
- A saturable hepatic uptake process governs ICG elimination, necessitating careful dosing.
