Basic & Clinical Pharmacology & Toxicology

Pharmacokinetic–Pharmacodynamic Relationships of Cognitive and Psychomotor Effects of Intravenous Buprenorphine Infusion in Human Volunteers

Mette L. Jensen

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark,

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Per Sjøgren,

Per Sjøgren

Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark,

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Richard N. Upton,

Richard N. Upton

Discipline of Anaesthesia and Intensive Care, Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia,

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David J. R. Foster,

David J. R. Foster

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia,

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Peter Bonde,

Peter Bonde

Department of Surgical Gastroenterology, Bispebjerg Hospital, Copenhagen, Denmark,

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Christian Graae,

Christian Graae

Department of Orthopedics, Hospital East, Køge, Denmark, and

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Ulrik Skram,

Ulrik Skram

Department of Neuroanaesthesia, Rigshospitalet, Copenhagen, Denmark

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Lene Stevner,

Lene Stevner

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark,

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Lona L. Christrup,

Lona L. Christrup

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark,

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Mette L. Jensen,

Mette L. Jensen

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark,

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Per Sjøgren,

Per Sjøgren

Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark,

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Richard N. Upton,

Richard N. Upton

Discipline of Anaesthesia and Intensive Care, Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia,

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David J. R. Foster,

David J. R. Foster

School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia,

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Peter Bonde,

Peter Bonde

Department of Surgical Gastroenterology, Bispebjerg Hospital, Copenhagen, Denmark,

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Christian Graae,

Christian Graae

Department of Orthopedics, Hospital East, Køge, Denmark, and

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Ulrik Skram,

Ulrik Skram

Department of Neuroanaesthesia, Rigshospitalet, Copenhagen, Denmark

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Lene Stevner,

Lene Stevner

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark,

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Lona L. Christrup,

Lona L. Christrup

Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark,

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First published: 28 June 2008

https://doi.org/10.1111/j.1742-7843.2008.00250.x

Citations: 25

Author for correspondence: Mette L. Jensen, Department of Pharmacology and Pharmacotherapy, The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark (fax +45 3530 6050, e-mail: [email protected]).

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Abstract

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.

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Volume103, Issue1

July 2008

Pages 94-101

Pharmacokinetic–Pharmacodynamic Relationships of Cognitive and Psychomotor Effects of Intravenous Buprenorphine Infusion in Human Volunteers

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Pharmacokinetic–Pharmacodynamic Relationships of Cognitive and Psychomotor Effects of Intravenous Buprenorphine Infusion in Human Volunteers

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