Dataset Information

Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial.

ABSTRACT:

Introduction

The effects of continuous infusions of ciprofol on its pharmacodynamic and pharmacokinetic properties and safety profiles in healthy Chinese subjects were evaluated.

Methods

In this open-label, randomized, two-way cross-over study, subjects received initial doses of continuous ciprofol/propofol as an infusion for 30 min in part 1 (n = 8) and a bolus dose in part 2 (n = 8) followed by maintenance infusions for a total of 4 h in part 1 and 12 h in part 2. Each subject participated in both parts with a washout time of at least 40 h.

Results

The safety and tolerability parameters of ciprofol were similar to those of propofol, and all treatment-emergent adverse events were mild. The incidences of injection pain and respiratory depression in subjects given ciprofol were lower than those receiving propofol. The pharmacokinetic parameters C_max, t_max, t_1/2, λz and MRT for ciprofol and propofol were similar, while CL, V_d and V_ss were statistically significantly different. Pharmacodynamic parameters including the Richmond Agitation Sedation Scale and bispectral index profiles of ciprofol were similar to those of propofol.

Conclusion

Ciprofol has potential for clinical application for continuous intravenous infusion to maintain sedation for 12 h with the same safety, tolerability and efficacy as propofol.

SUBMITTER: Hu C

PROVIDER: S-EPMC8523013 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial.

Hu Chao C Ou Xiaofeng X Teng Yi Y Shu Shiqing S Wang Ying Y Zhu Xiaohong X Kang Yan Y Miao Jia J

Advances in therapy 20210924 11

<h4>Introduction</h4>The effects of continuous infusions of ciprofol on its pharmacodynamic and pharmacokinetic properties and safety profiles in healthy Chinese subjects were evaluated.<h4>Methods</h4>In this open-label, randomized, two-way cross-over study, subjects received initial doses of continuous ciprofol/propofol as an infusion for 30 min in part 1 (n = 8) and a bolus dose in part 2 (n = 8) followed by maintenance infusions for a total of 4 h in part 1 and 12 h in part 2. Each subject p ...[more]

PMID: 34559359

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Project description:BackgroundCiprofol, a novel intravenous anesthetic, which has primarily been used for the induction and maintenance of general anesthesia in adults, is characterized by rapid onset, short duration of action, and quick and smooth recovery. However, the pharmacokinetic characteristics of continuous infusions and the correlation between the plasma concentration and the bispectral index (BIS) in elderly patients are still unknown.MethodIn this randomized, controlled study, thirty elderly patients (62-78 years old) undergoing elective gastrointestinal tumor resection were treated with propofol (N = 15) or ciprofol (N = 15) as sedatives during anesthesia. After induction, ciprofol/propofol was continuously infused intravenously until the end of the operation. Perioperative vital signs, injection pain, adverse events (AEs), BIS values, eyelid reflex disappearance times, and recovery times were recorded. The plasma concentrations of ciprofol and propofol were measured by liquid chromatography tandem mass spectrometry (LC‒MS/MS) and the pharmacokinetics were determined by noncompartmental analysis.ResultsBoth drugs caused a decrease in blood pressure and heart rate after induction. Eight cases (53. 3%) of hypotension and 3 cases (20%) of bradycardia occurred in the propofol group, while 8 cases (53. 3%) of hypotension and 5 cases (33. 3%) of bradycardia occurred in the ciprofol group. At intubation, the ciprofol group experienced fewer fluctuations in blood pressure than the propofol group. Ciprofol resulted in only one case (6.7%) of mild injection pain, less than that produced by propofol (10/15, 66.7%) (P < 0.05). Anesthesia induction was successfully completed with both drugs, and there were no significant differences in eyelash reflex disappearance or recovery time between the two groups. The plasma concentrations during maintenance were relatively stable in both groups (propofol 1.78 ± 0.67 μg/mL, ciprofol 0.71 ± 0.23 μg/mL), and a suitable depth of sedation was achieved with a BIS of 40-60. The pharmacokinetic (PK) parameters for ciprofol are listed as follows: Maximum Plasma Concentration (Cmax) 6.02 ± 2.13 μg/ml; Time to Maximum Concentration (Tmax) 0.18 ± 0.62 min; Apparent Volume of Distribution (Vz) 3.96 ± 0.84 L/kg; Total Clearance (CL) 0.83 ± 0.14 L/h/kg; Half-life (t½) 3.47 ± 1.85 h; Area Under the Curve (AUC) 5000 ± 900 L/h/kg; Terminal Elimination Rate Constant (λz) 0.23 ± 0.07 1/h. Similar to propofol, the plasma concentration of ciprofol was linearly correlated with the BIS.ConclusionCiprofol, a novel intravenous anesthetic, can be safely and effectively used in elderly patient continuous infusion with minimal injection pain. Plasma concentrations of ciprofol correlate well with BIS values, helping control sedation depth. For elderly patients undergoing gastrointestinal tumor surgery, an optimal maintenance dose of 0.8 mg/kg/h is recommended.Trial registrationThis clinical trial (registration No: ChiCTR2100047580, https://www.chictr.org.cn . The pre-registration date was June 20, 2021, and the review approval and official case solicitation began in December 2021; Retrospectively registered) was conducted in accordance with the World Medical Congress Declaration of Helsinki and Good Clinical Practice guidelines. All study subjects provided written informed consent.

Project description:IntroductionIntravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.MethodsSubjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.ResultsA total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m(2) P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).ConclusionsIn the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months.Trial registrationClinicalTrials.gov NCT01441245. Registered 23 September 2011.

Dataset Information

Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial.

Introduction

Methods

Results

Conclusion

Publications

Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial.

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