Diagnogreen Mechanism of Action

Pharmacology: Pharmacodynamics: Indocyanine green exhibits no pharmacological effects when administered IV and is suitable for liver function tests and chorioretinal angiography.
Absorption Wavelength: After administered IV, indocyanine green is rapidly bound to serum proteins and photochemically stabilized. The maximum absorption wavelength (785 nanometer in aqueous solution) rapidly increases to 805 nanometer in blood, which corresponds to the isosbestic point where the absorption curves of blood oxidized hemoglobin and reduced hemoglobin intersect one another. Measurement on this wavelength is not affected by blood oxygen saturation.
Pharmacokinetics: Blood Concentration: Plasma Concentration: After IV administration of indocyanine green at a dose of 0.25 mg/kg to healthy adults, the plasma concentration of the drug decreases in an exponential manner. The time-concentration curve shows the biphasic profile, with a rapid elimination phase within the 1st 15 min followed by a slow elimination phase. In healthy adults, the biological half-life (t_½) of indocyanine green is 3-4 min.
Serum Protein Binding: In healthy adults, 80% of indocyanine green in the serum is bound to globulin fractions. Indocyanine green is supposed to be bound mainly to α1-lipoprotein of globulin fractions. The affinity of this binding is much stronger than that of the binding between albumin and the pigment.
Distribution Reference (Animal Studies): In the mouse whole-body autoradiogram, uniform distribution of ³⁵S-indocyanine green in the systemic vascular system was shown. This was conspicuously distributed especially in the lung, heart, kidney and liver, 1 and 5 min after IV administration. At 15 min after the administration, the hepatic concentration of the compound achieved near maximum, and the compound was excreted into the gallbladder and distributed in the bile duct. A higher level of radioactivity was observed in the stomach and intestinal tract at 30 and 60 min after the administration. After 24 hrs, a slight amount of the tracer was detected in the liver and intestinal tract.
Metabolism: Indocyanine green is not supposed to undergo chemical or biological transformations in the body.
Excretion: After IV administration, indocyanine green is selectively taken up into the liver and then rapidly excreted into bile in an unchanged form. Enterohepatic circulation and urinary excretion were not observed.
Pharmacokinetic Change After Co-Administration with Fluorescein (Animal Studies): Pharmacokinetic parameters of indocyanine green (0.5 mg/kg IV) co-administered with fluorescein (10 mg/kg) in beagle dog shows no significant change compared to that after single administration.
Toxicology: Preclinical Safety Data: Single Dose Toxicity: LD₅₀ of IV injection are 64.3-72.8 mg/kg in mice, 87.1-97.9 mg/kg in rats and >90 mg/kg in dogs.
Repeated Dose Toxicity: In 1 month repeated IV dose study, 5 female rats in 20 mg/kg/day showed prone position, sedation, ptosis, lacrimation and respiration distress on day 5 or 6, of which 2 females were dead. No toxicity were noted in other groups (20 mg/kg/day in males, and 0.8 and 4 mg/kg/day in both sexes) or rabbits (5-50 mg/kg/day).
Reproduction Toxicity: No teratogenicity is noted in mice or rats (5-40 mg/kg/day ip). No genitoxicity, local irritation or carcinogenicity studies are conducted.