Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers
- Resource Type
- Authors
- Per Sjøgren; Lene Stevner; Christian Graae; Lona L. Christrup; David J. R. Foster; Peter Bonde; Ulrik Skram; Mette L. Jensen; Richard N. Upton
- Source
- Basicclinical pharmacologytoxicology. 103(1)
- Subject
- Adult
Male
Pharmacology
Toxicology
Cognition
Pharmacokinetics
Medicine
Distribution (pharmacology)
Humans
Psychological testing
Infusions, Intravenous
Psychomotor learning
Psychological Tests
business.industry
Neuropsychology
General Medicine
Buprenorphine
Analgesics, Opioid
Nonlinear Dynamics
Anesthesia
Pharmacodynamics
business
Psychomotor Performance
medicine.drug
Half-Life
- Language
- ISSN
- 1742-7843
The main objective of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the effects of buprenorphine on cognitive functioning in healthy volunteers. Twenty-three male volunteers received 0.6 mg buprenorphine as an intravenous infusion over 150 min. The cognitive and psychomotor performance was evaluated before and at various times after drug administration by a test battery consisting of trail-making test for visual information processing, finger-tapping test for psychomotor speed, and continuous reaction time for attention. Non-linear mixed effect modelling was used in the analysis of the PK/PD relationships. Buprenorphine caused significant deficits in cognitive and psychomotor functioning. The time course of cognitive and psychomotor impairment was found to have a slow distribution to the biophase from plasma with PK/PD models involving an effect compartment providing the best descriptions of the time course of the data. The values for half-life of biophase equilibration were consistent between the neuropsychological tests in the range of 66.6-84.9 min. The time to onset and duration of the cognitive and psychomotor impairment of buprenorphine was determined by a slow distribution to the biophase.