The influence of hypothermia on the disposition of fentanyl--human and animal studies.
The effect of hypothermia on the disposition of fentanyl was evaluated in 18 children undergoing corrective cardiac surgery. They received a bolus of fentanyl followed by a continuous infusion which was stopped when cardiopulmonary bypass was established and profound hypothermia was achieved (18 degrees C-25 degrees C). Fentanyl plasma concentration remained essentially unchanged during hypothermia (6.45 ng/ml 5 min into hypothermia and 5.26 ng/ml 100-140 min later; p greater than 0.1). In subsequent experiments, the effect of hypothermia on the pharmacokinetics of fentanyl was studied in 4 piglets serving as their own controls. Both distribution volume (Vz) and total body clearance (CL) were significantly smaller during hypothermia. Our studies indicate that being a drug with a large distribution volume and a high hepatic extraction ratio, both CL and Vz are significantly reduced by hypothermia-induced hypoperfusion. In addition, TBC is influenced by the temperature-dependent hepatic metabolism of fentanyl.
D000293:Adolescent; D000818:Animals; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D005283:Fentanyl / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007036:Hypothermia, Induced; D007223:Infant; D007700:Kinetics; D008102:Liver Circulation; D013552:Swine
D005283:Fentanyl