European Journal of Clinical Pharmacology

, Volume 35, Issue 3, pp 295–303

Pharmacokinetics of biliary excretion in man. VI. Indocyanine green

Authors

  • D. K. F. Meijer
    • Departments of Pharmacology and Therapeutics and Pharmacology and Clinical PharmacologyUniversity of Groningen
  • B. Weert
    • Departments of Pharmacology and Therapeutics and Pharmacology and Clinical PharmacologyUniversity of Groningen
  • G. A. Vermeer
    • Departments of Pharmacology and Therapeutics and Pharmacology and Clinical PharmacologyUniversity of Groningen
Originals

DOI: 10.1007/BF00558268

Cite this article as:
Meijer, D.K.F., Weert, B. & Vermeer, G.A. Eur J Clin Pharmacol (1988) 35: 295. doi:10.1007/BF00558268

Summary

The pharmacokinetics of Indocyanine Green (ICG) has been studied in 15 patients given 0.5, 1.0 and 2.0 mg · kg−1. The plasma disappearance and biliary excretion rate were measured in patients with tightly fitting catheters under slight negative pressure in order to achieve complete collection of bile. Recovery of unchanged ICG in bile over 18 h after the i.v. injection was 80% of the dose in all three dose groups.

Plasma disappearance in all 3 groups was biphasic, showing an initial phase with a t1/2 of 3–4 min and a secondary phase with a dose-dependent apparent t1/2 of 67.6, 72.5 and 88.7 min, respectively. After 0.5 and 1.0 mg · kg−1 the biliary excretion rate curves showed an ascending phase with a mean t1/2 of 5 min and a descending phase with a mean t1/2 of 72 min. It was inferred that the secondary component of the plasma-decay mainly reflected the biliary excretion rate. After 2.0 mg · kg−1 in some patients the biliary excretion curve showed features of saturation; the t1/2 of the descending phase ranged from 73 to 440 min, and the time of maximal excretion was increased from 1.3 to 2.7 h after injection, whilst the mean maximal excretion rate was in the same range as the excretion rate after the 1.0 mg · kg−1 dose. The non-linear pharmacokinetics was only moderately reflected in the measured plasma disappearance patterns. Two compartment analysis of the plasma levels indicated a clearance of 230–260 ml · min−1, whereas the clearance conventionally calculated from the initial t1/2 was 475 ml · min−1. The volume of the central compartment in 70 kg patients was 2.31, which is about the plasma volume. The fictive volume of distribution in the liver (V2) was 70–90 l, indicating marked hepatic storage of ICG. This was probably due to the very low liver-to-plasma transport rate (k21) of 0.006–0.10 min−1. Thus, the biliary excretion of ICG can be quantified by 2-compartment pharmacokinetic analysis of plasma disappearance curves, including a secondary phase. The latter, slow component was apparent at very low plasma levels due to the marked hepatic storage, and it was also influenced by retention of small amounts of impurities or degradation products. Improved detectability of this phase cannot simply be obtained by increasing the dose, since at doses exceeding 1.0 mg · kg−1 non-linear elimination may complicate the pharmacokinetic analysis.

Key words

indocyanine greenpharmacokineticsbiliary excretionliver function test

Copyright information

© Springer-Verlag 1988