Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers.
OBJECTIVE
The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only.


METHODS
Twenty-three healthy male volunteers aged 21-40 years received 0.6 mg buprenorphine by means of an i.v. infusion over a 150-min period. The plasma concentration-time profiles up to 24 h post-administration of the infusion were subjected to population pharmacokinetic modelling using NONMEM: software.


RESULTS
A three-compartment model best described the plasma concentration-time course. Body weight was found to be a significant covariate for elimination clearance in a linear fashion. Inter-individual variability (coefficient of variation) was estimable for apparent clearance (CL, 23.5%), central distribution volume (V(1), 81.8%), peripheral distribution volume 1 (V(2), 23.7%) and inter-compartmental clearances between V(1) and V(2) (Q(2), 34.8%). Models using parameters derived from previous published data obtained after an i.v. bolus of buprenorphine were found to overestimate the measured buprenorphine concentrations during the course of the i.v. infusion and to underpredict those following the end of the infusion.


CONCLUSIONS
Most parameters describing the disposition of buprenorphine in the volunteers showed only moderate inter-subject variability. However, the parameters differed from those previously reported for i.v. bolus administration. We conclude that pharmacokinetic parameter estimates obtained from the appropriate study in accordance to the mode of administration should be used in the design of dose regimens of buprenorphine.
Jensen
Mette L
ML
Department of Pharmacology and Pharmacotherapy, The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. mlj@farma.ku.dk
Foster
David J R
DJ
Upton
Richard N
RN
Kristensen
Kim
K
Hansen
Steen H
SH
Jensen
Niels-Henrik
NH
Nielsen
Bettina N
BN
Skram
Ulrik
U
Villesen
Hanne H
HH
Christrup
Lona
L
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003718:Denmark; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008954:Models, Biological; D011159:Population Surveillance
D000701:Analgesics, Opioid; D002047:Buprenorphine