Population pharmacokinetics and analgesic potency of fentanyl in surgical patients

Abstract

Background: We aimed to characterize the population pharmacokinetics of fentanyl in surgical patients and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of intravenous fentanyl in patients after major abdominal open surgery. We also calculated the equianalgesic concentration ratio of oxycodone to fentanyl by using the median MEAC value of oxycodone observed in our previous study. Methods: In the pharmacokinetic study, patients received an intravenous bolus of 100 g fentanyl during operation, and arterial blood was sampled at pre-set intervals. In the analgesic-potency study, patients were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain) in the postanesthesia care unit. The first blood sample was obtained when wound pain was rated as ≥ 3 at rest and ≥ 5 during compression. Then, 50 g fentanyl was administered every 10 min until the pain intensity had decreased to < 3 at rest and < 5 during compression, at which point the second blood was sampled and the 1st MEAC of fentanyl was measured. The same procedure was repeated to obtain a third sample (MEC) and fourth sample (2nd MEAC). Results: In the population pharmacokinetic study (n = 30), the plasma concentration of fentanyl over time was well-described by the three-compartment mammillary model using an allometric expression. In the analgesic-potency study (n = 30), the median MEC was 0.72 ng/ml, and the MEACs were 0.97 ng/ml and 1.04 ng/ml at 1st and 2nd measurement, respectively. Conclusion: These results provide a scientific basis for the use of fentanyl for acute postoperative pain management in surgical patients. The equianalgesic concentration ratio and equipotent ratio of oxycodone to fentanyl were 75:1 and 100:1, respectively.