Drug‐drug interaction of ciprofol injectable emulsion with mefenamic acid capsules in healthy subjects

• Published in: British journal of clinical pharmacology Vol. 89; no. 10; pp. 3165 - 3174
• Main Authors: Yang, Dandan, Hu, Yin, Ruan, Zourong, Jiang, Bo, Wang, Haiying, Xu, Yichao, Hu, Mengyue, Yan, Min, Lou, Honggang
• Format: Journal Article
• Language: English
• Published: England 01.10.2023
• Subjects: pharmacokinetics; drug-drug interaction; pharmacodynamics; mefenamic acid; ciprofol
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.15822

To investigate the drug-drug interaction (DDI) of ciprofol injectable emulsion and mefenamic acid capsules in healthy subjects. Twenty healthy subjects were enrolled in this single-centre, open-label, two-period DDI study. Ciprofol (0.4 mg kg ) 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). Compared 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 (C ), area under the plasma concentration-time curve calculated from 0 to the last measurement point (AUC ) and AUC to infinity (AUC ) 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. Mefenamic 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.