Pharmacokinetics of Intraperitoneal Lidocaine for Sustained Postoperative Analgesia in Adults.

Abstract

Background and objective: Intraperitoneal lidocaine is an emerging strategy for analgesia following abdominal surgery but its pharmacokinetics are poorly quantified. We aimed to develop a pharmacokinetic model for unbound and total lidocaine by intraperitoneal and intravenous routes.

Methods: Unbound and total lidocaine concentrations, and pain scores (visual analogue score 0-10) were from a published randomized control trial of adults (n = 56) undergoing laparoscopic colon resection. Participants received intravenous or intraperitoneal lidocaine (2 mg/kg bolus then 1.5 mg/kg/h infusion) for 72 h postoperatively. Data were pooled with literature-derived alpha-1-acid glycoprotein concentrations (AAG) to support total lidocaine modelling. Unbound kinetics were described using compartmental models with first order absorption between intraperitoneal and plasma compartments. A turnover model described AAG kinetics with constant binding to lidocaine. An inhibitory pharmacodynamic model was explored to link concentration to pain scores.

Results: Maximum lidocaine concentrations after intraperitoneal administration were means (range) of 3.0 (0.4-4.5) mg/L total and 0.6 (0.1-0.9) mg/L unbound. Intraperitoneal absorption was incomplete (bioavailability = 0.66, 95% confidence interval (CI) 0.6-0.76) with a half-time of 0.5 (0.4-0.8) h. A two-compartment model with first order elimination fit best, with unbound clearance 121 (108-136) L/h/70 kg. The binding constant to AAG (K_D) was 2.98 (2.69-3.35) µmol/L. A pharmacodynamic model with C₅₀ of 0.21 mg/L and maximal reduction (E_max) of 6 units captured pain scores and was used to simulate dosing strategies.

Conclusions: A third of the intraperitoneal dose did not reach the central compartment and absorption took ~2 h. Simulations show that 2 mg/kg/h intraperitoneal infusion achieves a 5-point pain score reduction within ~36 min.