PMID- 37309663
OWN - NLM
STAT- MEDLINE
DCOM- 20230915
LR  - 20230929
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 89
IP  - 10
DP  - 2023 Oct
TI  - Drug-drug interaction of ciprofol injectable emulsion with mefenamic acid 
      capsules in healthy subjects.
PG  - 3165-3174
LID - 10.1111/bcp.15822 [doi]
AB  - AIMS: To investigate the drug-drug interaction (DDI) of ciprofol injectable 
      emulsion and mefenamic acid capsules in healthy subjects. METHODS: Twenty 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). RESULTS: 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(max) ), area under the plasma 
      concentration-time curve calculated from 0 to the last measurement point 
      (AUC(0-last) ) and AUC to infinity (AUC(0-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. CONCLUSIONS: 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.
CI  - (c) 2023 British Pharmacological Society.
FAU - Yang, Dandan
AU  - Yang D
AUID- ORCID: 0009-0007-7168-0364
AD  - Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Hu, Yin
AU  - Hu Y
AD  - Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Ruan, Zourong
AU  - Ruan Z
AD  - Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Jiang, Bo
AU  - Jiang B
AD  - Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Wang, Haiying
AU  - Wang H
AD  - Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Xu, Yichao
AU  - Xu Y
AD  - Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Hu, Mengyue
AU  - Hu M
AD  - Sichaun Haisco Pharmaceutical Co., Ltd., Chengdu, Sichuan, China.
FAU - Yan, Min
AU  - Yan M
AD  - Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
FAU - Lou, Honggang
AU  - Lou H
AD  - Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang 
      University, School of Medicine, Hangzhou, Zhejiang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230701
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 367589PJ2C (Mefenamic Acid)
RN  - 0 (Emulsions)
RN  - 0 (Capsules)
SB  - IM
MH  - Humans
MH  - *Mefenamic Acid/adverse effects
MH  - Healthy Volunteers
MH  - Emulsions
MH  - Capsules
MH  - Drug Interactions
MH  - Cross-Over Studies
MH  - Area Under Curve
OTO - NOTNLM
OT  - ciprofol
OT  - drug-drug interaction
OT  - mefenamic acid
OT  - pharmacodynamics
OT  - pharmacokinetics
EDAT- 2023/06/13 06:42
MHDA- 2023/09/15 06:42
CRDT- 2023/06/13 05:25
PHST- 2023/05/27 00:00 [revised]
PHST- 2023/03/19 00:00 [received]
PHST- 2023/06/02 00:00 [accepted]
PHST- 2023/09/15 06:42 [medline]
PHST- 2023/06/13 06:42 [pubmed]
PHST- 2023/06/13 05:25 [entrez]
AID - 10.1111/bcp.15822 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2023 Oct;89(10):3165-3174. doi: 10.1111/bcp.15822. Epub 2023 
      Jul 1.