Performance of Two Different ke0s in the Same Pharmacokinetic Propofol Model

Unconsciousness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01011192
• Other study ID #: RFS 02
• Status: Completed
• Phase: N/A
• First received: November 10, 2009
• Last updated: November 12, 2009
• Start date: September 2009
• Est. completion date: November 2009

Study information

• Verified date: November 2009
• Source: Centro Medico Campinas
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Unconsciousness

Locations

Country	Name	City	State
Brazil	Hospital Santa Sofia	Campinas	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Centro Medico Campinas	Hospital Santa Sofia Ltda

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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):107-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Propofol effect-site concentration (Ce) during the loss and recovery of consciousness with fast and slow keo.		20 minutes