Performance of Two Different ke0s in the Same Pharmacokinetic Propofol Model

NCT ID: NCT01011192

Last Updated: 2009-11-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2009-11-30

Brief Summary

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

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.

Conditions

Unconsciousness

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ke0 of 0.26 min-1

Individual volunteers using Marsh's pharmacokinetic target-controlled infusion model with ke0 of 0.26 min-1 (Asena PK® - Cardinal Health)

No interventions assigned to this group

ke0 of 1.21 min-1

Individual volunteers using Marsh's pharmacokinetic target-controlled infusion model with ke0 of 1.21 min-1 (Primea Orchestra® - Fresenius-Kabi basis)

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Hospital Santa Sofia Ltda

UNKNOWN

Sponsor Role: collaborator

Centro Medico Campinas

OTHER

Sponsor Role: lead

Responsible Party

Hospital Santa Sofia Ltda

Principal Investigators

Ricardo F Simoni, MD

Role: PRINCIPAL_INVESTIGATOR

Centro Medico Campinas

Locations

Hospital Santa Sofia

Campinas, São Paulo, Brazil

Countries

Brazil

References

Iwakiri H, Nishihara N, Nagata O, Matsukawa T, Ozaki M, Sessler DI. Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening. Anesth Analg. 2005 Jan;100(1):107-110. doi: 10.1213/01.ANE.0000139358.15909.EA.

Reference Type: RESULT

PMID: 15616062 (View on PubMed)

Other Identifiers

RFS 02

Identifier Type: -

Identifier Source: org_study_id