Optimal Timing of Intravenous Acetaminophen Administration for Postoperative Analgesia

Acetaminophen (APAP) is widely used as an analgesic for postoperative pain relief. However, the pharmacokinetic-pharmacodynamic (PK-PD) properties of intravenous APAP administration remain unclear. We developed a PK-PD model in adult volunteers.

APAP (1 g) was intravenously administered to 15 healthy volunteers. The pain equivalent current (PEC) was then measured using the pulse current, corresponding to the quantitative value of pain perception. The PK model was developed using a 2-compartment model, and the PD model was developed using a linear model and an effect compartment model.

APAP plasma concentration peaked just administration, whereas PEC significantly increased at 90 minutes and lasted through the experimental period (300 minutes). APAP plasma concentrations and PEC were processed for use in the PK-PD model. The developed PK-PD model delineates the analgesic effect profile, which peaked at 188 minutes and lasted until 327 minutes.

We developed the PK/PD model for APAP administered intravenously. The analgesic effect can be expected ∼90 minutes after administration and to last >5 hours. It is suggested that APAP be administered ∼90 minutes prior to the onset of anticipated postoperative pain.