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The effect of pentobarbitone anaesthesia and hypothermia on the hepatic clearance of indocyanine green and S(−)‐acenocoumarol in the rat

The effect of pentobarbitone anaesthesia and the effect of hypothermia associated with the anaesthesia on the blood clearance of indocyanine green (ICG) and of S(−)‐acenocoumarol (AC) was investigated in male Wistar rats using the constant rate infusion technique. During anaesthesia, body temperature was regulated by heat supply. At normothermia (rectal temperature of 37.5 °C), pentobarbitone anaesthesia decreased ICG clearance from 8.0 ± 1.7 ml min−1 (mean ± s.e.m., n = 3) in the conscious state to 4.3 ± 0.6 ml min−1 and AC clearance from 4.9 ± 0.4 ml min−1 to 3.4 ± 0.3 ml min−1. Hypothermia further reduced the clearances of the compounds to 0.9 ± 0.1 and 2.5 ± 0.2 ml min−1 for ICG and AC, respectively. The effect of hypothermia was reversible. The results show that pharmacokinetic constants obtained in the anaesthetized animal may differ greatly from those in the conscious one. If pharmacokinetic experiments are performed in the anaesthetized animal, body temperature should be controlled and a slight hyperthermia is most favourable. Our pharmacokinetic data on ICG seriously question the use of this drug to estimate liver blood flow in the rat.