AbstractAimsTo investigate the drug‐drug interaction (DDI) of ciprofol injectable emulsion and mefenamic acid capsules in healthy subjects.MethodsTwenty healthy subjects were enrolled in this single‐centre, open‐label, two‐period DDI study. Ciprofol (0.4 mg kg−1) was administered as a single dose on days 1 and 5. A 500‐mg oral loading dose of mefenamic acid was given on day 4 followed by a 250‐mg maintenance dose every 6 h (a total of eight doses). Blood samples for pharmacokinetic analyses were collected. Depth of anaesthesia was monitored using the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale and Bispectral Index scores (BISs).ResultsCompared with administration of ciprofol alone, administration with mefenamic acid showed no significant difference in exposure. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for maximum plasma concentration (Cmax), area under the plasma concentration‐time curve calculated from 0 to the last measurement point (AUC0‐last) and AUC to infinity (AUC0‐inf) were 91.6% (86.5‐96.9%), 103.3% (100.3‐106.4%) and 107.0% (101.2‐113.2%), respectively. The MOAA/S and BIS curves for the two treatment periods essentially coincided, indicating that the anaesthesia effect of ciprofol was not affected by mefenamic acid. Seven subjects (35%) reported eight adverse events (AEs) when ciprorol was administered alone and 12 subjects (60%) reported 18 AEs when ciprofol was administered in combination with mefenamic acid. All AEs were mild.ConclusionsMefenamic acid, a UGT1A9 inhibitor, had no significant effect on the pharmacokinetics and pharmacodynamics of ciprofol in healthy subjects. Ciprofol was safe and well tolerated when administered with mefenamic acid.