[Disposition of fentanyl in human blood]

Plasma protein binding and uptake of fentanyl by erythrocytes was studied in a group of 30 healthy patients of both sexes (aged 4-84 years), undergoing orthopaedic or minor surgical operations. Using equilibrium dialysis (24 h, 37 degrees C, phosphate buffer pH 7.4 containing fentanyl 5 ng/ml) the protein bound fraction was found to be 72.4% +/- 7.9 (mean +/- standard deviation). Proteins in the plasma of children or elderly patients bound to a slightly higher degree as compared with the group of medium age, while no differences between sexes were observed. The addition of various intravenous anaesthetic drugs in a therapeutic concentration range did not alter plasma protein binding seriously. There seems to be a correlation between fentanyl plasma protein binding and the plasma content of acid alpha-1-glycoproteins. Human erythrocytes were found to equilibrate very rapidly with plasma fentanyl, the partition coefficient being almost unity. Distribution into the red cells was not influenced by adding intravenous anaesthetics or plasma expanders to the blood samples, nor was it altered by changes of pH or temperature. Storage of fentanyl did not modify erythrocyte morphology even at high concentrations, as indicated by normal MCV or MCHC. Fentanyl was found not to be metabolized in human whole blood, haemolysate or plasma. The activity of serum enzymes commonly used in routine diagnosis was not influenced by fentanyl concentrations in a range up to 1,000 ng/ml.