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Compartmental pharmacokinetics of nefopam during mild hypothermia


Podranski, T; Bouillon, T W; Riva, T; Kurz, A M; Oehmke, M J (2012). Compartmental pharmacokinetics of nefopam during mild hypothermia. British Journal of Anaesthesia, 108(5):784-791.

Abstract

Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam. Methods We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling. Results A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (se): V1=24.13 (2.8) litre; V2=183.34 (13.5) litre; Clel=0.54 (0.07) litre min−1; Cldist=2.84 (0.42) litre min−1]. Conclusions The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermia

Abstract

Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam. Methods We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling. Results A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (se): V1=24.13 (2.8) litre; V2=183.34 (13.5) litre; Clel=0.54 (0.07) litre min−1; Cldist=2.84 (0.42) litre min−1]. Conclusions The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermia

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Anesthesiology and Pain Medicine
Uncontrolled Keywords:anaesthesia, hypothermia, nefopam, pharmacokinetics, shivering, thermoregulation
Language:English
Date:1 May 2012
Deposited On:19 Nov 2018 16:39
Last Modified:15 Apr 2021 14:51
Publisher:Elsevier
ISSN:0007-0912
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/bja/aer517
PubMed ID:22331396

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