Effects of Voriconazole on the Safety, Pharmacokinetics and Pharmacodynamics of Ciprofol (HSK3486), a Novel Intravenous Anaesthetic, in Healthy Participants: A Prospective, Randomized, Crossover Clinical Trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Yicong Bian,1,2,* Tao Hu,1,2,* Qingqing Deng,1,3,* Sheng Ma,1,2 Yongyi Jiao,4 Jian Shi,1,2 Nan Jiang,5 Mengyue Hu,6 Yongrui Wang,6 Xiao Liu,6 Zihan Zhang,7 Chenrong Huang,1,2 Hua Zhang,1,2 Liyan Miao1,2 1Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University, Suzhou, People’s Republic of China; 3College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China; 4Department of Anesthesiology, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 6Department of Clinical Pharmacology, Haisco Pharmaceutical Group Co. Ltd., Chengdu, People’s Republic of China; 7Department of Pharmaceutical Sciences, Xi’an Jiaotong Liverpool University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyan Miao, Department of Pharmacy, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, People’s Republic of China, Tel +86 051267972858, Email [email protected]; [email protected] Hua Zhang, Department of Pharmacy, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, People’s Republic of China, Tel +86 051267972858, Email [email protected]: Ciprofol, a novel intravenous anaesthetic, is an analogue of propofol with superior anaesthetic efficacy. Ciprofol is widely metabolized in humans, and cytochrome P450 enzymes (CYPs) are involved in its metabolism. However, the drug‒drug interactions between ciprofol and drugs that may affect CYPs remains unclear. Therefore, we investigated the effects of voriconazole on the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ciprofol.Methods: A randomized, two-period, two-sequence, crossover study was conducted in healthy participants who received a single intravenous dose of 0.4 mg/kg ciprofol (treatment A) and 0.4 mg/kg ciprofol after multiple doses of voriconazole (treatment B), a multiple inhibitor of CYP3A4/5, CYP2B6 and CYP2C9/19, in either sequence AB or sequence BA.Results: MOAA/S-time curves revealed that the participants were anaesthetized rapidly (2.01 min versus 1.82 min) and recovered smoothly (11.58 min versus 11.64 min) after receiving ciprofol either alone or combined with voriconazole. The mean BISpeak values were 41.1 and 44.4, respectively. Voriconazole slightly increased the plasma AUC of ciprofol, but the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for Cmax, AUC0-t and AUC0-∞ of plasma ciprofol were still in the range of 80%-125%, which demonstrated pharmacokinetic bioequivalence between the two treatments. No serious adverse effects were reported.Conclusion: Ciprofol was well tolerated in combination with voriconazole, and the anaesthetic effect was satisfactory. The dose of ciprofol is suggested not be adjusted in patients receiving the CYP inhibitor voriconazole based on the PK, PD and safety characteristics.Trial Registration: Clinicaltrials.gov, NCT04145583, registered on 25 October 2019.Keywords: ciprofol, intravenous anaesthetic, drug-drug interaction, pharmacokinetics, pharmacodynamics, safety
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7120439889
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