Performance of Two Different ke0s in the Same Pharmacokinetic Propofol Model

Study Overview
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Brief Summary
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The aim of this study was to assess the clinical performance of two different ke0s (fast and slow) in terms of propofol effect-site concentration (Ce) during the loss and recovery of consciousness, using Marsh's pharmacokinetic model.The hypothesis to be tested was that the Ce of propofol predicted by the slow ke0 in the loss and recovery of consciousness is similar, differently from the fast ke0.

Detailed Description
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Introduction: The ke0 can be defined as the proportional variation of the gradient of concentration between the plasma and the effect-site in relation to the unit of time. Theoretically, the higher the value of the ke0, the faster the drug enters the effect-site. Therefore, drugs with short T½ke0 have high ke0s and fast onset of action. The aim of this study was to assess the clinical performance of two different ke0s (fast and slow) in terms of propofol effect-site concentration (Ce) during the loss and recovery of consciousness, using Marsh's pharmacokinetic model. Method: Twenty healthy male adult volunteers participated in this study. Propofol was first administered to the individual volunteer using Marsh's pharmacokinetic target-controlled infusion model with ke0 of 1.21 min-1 and, on another opportunity, with the same pharmacokinetic model but ke0 of 0.26 min-1. Propofol was infused in plasma target-concentration of 3.0 µg.mL-1. Loss and recovery of consciousness was defined as response of the volunteer to verbal stimulus. The Ce was registered at the moments of loss and recovery of consciousness. Results: At loss and recovery of consciousness, propofol Ce means predicted by the fast ke0 were different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL-1, respectively, p < 0.0001), whereas with the slow ke0 the predicted Ce means were similar (2.20 ± 0.70 and 2.13 ± 0.43 µg.mL-1, respectively, p = 0.5425). Conclusion: It can be concluded that slow ke0 (0.26 min-1) incorporated into Marsh's pharmacokinetic model showed better clinical performance than fast ke0 (1.21 min-1), since the predicted effect-site concentrations of propofol at loss and recovery of consciousness were similar.

Official Title
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Performance of Two Different Ke0s in the Same Pharmacokinetic Propofol Model. Study on Loss and Recovery of Consciousness

Conditions
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Unconsciousness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy male adult between 20 and 45 years old Exclusion Criteria: use of alcohol or illicit drugs chronic use of H2 inhibitors and tricyclic antidepressants of calcium channel blockers hypersensitivity to the drugs used in the experimental protocol.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ke0 of 0.26 min-1<br>Individual volunteers using Marsh's pharmacokinetic target-controlled infusion model with ke0 of 0.26 min-1 (Asena PK® - Cardinal Health) | |
| ke0 of 1.21 min-1<br>Individual volunteers using Marsh's pharmacokinetic target-controlled infusion model with ke0 of 1.21 min-1 (Primea Orchestra® - Fresenius-Kabi basis) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Propofol effect-site concentration (Ce) during the loss and recovery of consciousness with fast and slow keo. |  | 20 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravenous anesthesia, propofol, pharmacokinetic model, Monitoring, bispectral index.