Population pharmacodynamic model for ketorolac analgesia

Area of Science:

• Pharmacology
• Clinical Pharmacology
• Pharmacometrics

Background:

• Analyzing complex analgesic trial data with repeated measurements and ordered categorical responses presents challenges.
• Nonrandom censoring due to rescue medication use requires sophisticated modeling approaches.

Purpose of the Study:

• To develop a population pharmacokinetic-pharmacodynamic (PK/PD) model for intramuscular ketorolac in moderate to severe postoperative pain.
• To characterize pain relief scores and time to remedication.
• To identify the optimal initial dose for effective pain management.

Main Methods:

• A population PK/PD model was derived using data from 522 patients receiving placebo or varying doses of ketorolac (10-90 mg IM).
• Pain relief was assessed using a five-category ordinal scale.
• Pharmacokinetic data from 85 subjects were analyzed.
• Models were fitted using the NONMEM program.

Main Results:

• Pain relief followed an Emax model dependent on drug concentration and time, with a placebo effect.
• The EC50 was 0.37 mg/L and the keo half-life for pain relief was 24 minutes.
• Simulations indicated that 30 mg IM ketorolac achieved adequate pain relief in 50% of patients within 27 minutes, with 70% experiencing sustained relief for 6 hours.

Conclusions:

• A population PK/PD model for intramuscular ketorolac's analgesic efficacy was successfully derived.
• The model supports the use of 30 mg IM ketorolac as the optimal initial dose for postoperative pain.
• The study provides a quantitative basis for optimizing ketorolac dosing strategies.