Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 77, Issue 6, Pages 1027-1038Publisher
WILEY
DOI: 10.1111/bcp.12291
Keywords
analgesia; elderly; logistic regression; nefopam; population pharmacokinetics; renal impairment
Categories
Funding
- Regional Clinical Research Program of Reims University Hospital [PHRC 2004-R11-07]
Ask authors/readers for more resources
Aims Nefopam is a nonmorphinic central analgesic, for which no recommendation exists concerning adaptation of regimen in aged patients with or without renal impairment. The objective was to describe the pharmacology of nefopam in aged patients to obtain guidelines for practical use. Methods Elderly patients (n = 48), 65-99 years old, with severe or moderate renal impairment or with normal renal function, were recruited. Nefopam (20mg) was administered as a 30min infusion postoperatively. Simultaneously, a 1min intravenous infusion of iohexol was performed, in order to calculate the glomerular filtration rate. Blood samples were drawn to determine nefopam, desmethyl-nefopam and iohexol plasma concentrations. Nefopam and desmethyl-nefopam concentrations were analysed using a nonlinear mixed-effects modelling approach with Monolix version 4.1.3. The association between pharmacokinetic parameters and treatment response was assessed using logistic regression. Results A two-compartment open model was selected to describe the pharmacokinetics of nefopam. The typical population estimates (between-subject variability) for clearance, volume of distribution, intercompartmental clearance and peripheral volume were, respectively, 17.3lh-1 (53.2%), 114l (121%), 80.7lh-1 (79%) and 208l (63.6%). Morphine requirement was related to exposure of nefopam. Tachycardia and postoperative nausea and vomiting were best associated with maximal concentration and the rate of increase in nefopam plasma concentration. Conclusions We identified the nefopam pharmacokinetic predictors for morphine requirement and side-effects, such as tachycardia and postoperative nausea and vomiting. In order to maintain morphine sparing and decrease side-effects following a single dose of nefopam (20mg), simulations suggest an infusion time of >45min in elderly patients with or without renal impairment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available