Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers.
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.
Jensen
Mette L
ML
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark. mlj@farma.ku.dk
Sjøgren
Per
P
Upton
Richard N
RN
Foster
David J R
DJ
Bonde
Peter
P
Graae
Christian
C
Skram
Ulrik
U
Stevner
Lene
L
Christrup
Lona L
LL
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*
D000701:Analgesics, Opioid; D002047:Buprenorphine