A randomized controlled trial depicted that a novel Ketorolac tromethamine formulation (NTM-001) administered as a 12.5 mg intravenous (IV) bolus followed by a continuous infusion of 3.5 mg/h through a standard hospital infusion pump, could serve as an alternative to opioids for addressing acute postoperative pain. This first-in-man study aimed to assess the appropriate dosage, safety, and efficacy of NTM-001 to tackle postoperative pain compared to a standard regimen, addressing the urgent need for a nonopioid analgesic.

Researchers compared the effects of a 12.5 mg IV bolus followed by a continuous 3.5 mg/h infusion over 24 hours with the traditional approach of a 30 mg IV bolus of generic Ketorolac every 6 hours. The evaluation included pharmacokinetic (PK) measures and safety profiles based on a specified product profile. Graphical overlay and model-based comparisons were utilized to analyze the concentration-time curve. In an open-label crossover design, a cohort of 28 healthy adults (50% men) received NTM-001 and bolus dosing.

The observed plasma concentrations closely matched with predicted values, exhibiting no outliers. Graphical overlay comparisons indicated minimal between-subject variability, aligning well with projected concentration-time targets. The PK base models, incorporating preliminary PK data from both the NTM-001 and bolus groups, illustrated median profiles within 95% prediction limits, and no revisions to the models were necessary.

Aligned with the patterns of serum concentration over time, the pain relief scores stayed within the expected ranges. However, the initial scores for NTM-001 surpassed the targeted profile, possibly attributed to slightly elevated initial serum Ketorolac concentrations compared to predictions. The 24-hour pain relief projection for NTM-001, derived from the median Ketorolac pain relief versus time curve, was approximately 6% lower than the targeted pain relief. Both treatments displayed a good tolerability profile, and there were no instances of participants discontinuing treatment due to adverse events.

The PK parameters for NTM-001 and the comparator bolus closely aligned with the modeling targets, requiring no modifications to the base model. The absence of outliers and minimal intersubject variability was observed. Hence, NTM-001, administered as a 12.5 mg IV bolus followed by 3.5 mg/h infusion, aligns with predicted pharmacokinetic targets, offers effective pain alleviation with low variability, and may serve as a safe nonopioid option for postoperative pain mitigation.