title: Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers.
abstract: 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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark. mlj@farma.ku.dk
authors.forename: Mette L
authors.initials: ML
authors.lastname: Jensen
authors.forename: Per
authors.initials: P
authors.lastname: Sjøgren
authors.forename: Richard N
authors.initials: RN
authors.lastname: Upton
authors.forename: David J R
authors.initials: DJ
authors.lastname: Foster
authors.forename: Peter
authors.initials: P
authors.lastname: Bonde
authors.forename: Christian
authors.initials: C
authors.lastname: Graae
authors.forename: Ulrik
authors.initials: U
authors.lastname: Skram
authors.forename: Lene
authors.initials: L
authors.lastname: Stevner
authors.forename: Lona L
authors.initials: LL
authors.lastname: Christrup
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002047:Buprenorphine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D017711:Nonlinear Dynamics; D011581:Psychological Tests; D011597:Psychomotor Performance / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine