当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil.

Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil.

Abstract：

PURPOSE:Pharmacodynamic studies of naloxone require opioid agonism. Steady state condition may be achieved by remifentanil TCI (target controlled infusion). Opioid agonism can be measured by pupillometry. It is not known whether there are arteriovenous concentration differences for naloxone. The aim was thus to further develop a model for studying pharmacokinetic/pharmacodynamic aspects of naloxone and to explore whether a significant arteriovenous concentration difference for naloxone in humans was present. METHODS:Relevant authorities approved this study. Healthy volunteers (n = 12) were given 1.0 mg intravenous (IV) naloxone after steady state opioid agonism was obtained by TCI of remifentanil (1.3 ng/ml). Opioid effect was measured by pupillometry. Arterial and venous samples were collected simultaneously before and for 2 h after naloxone administration for quantification of naloxone and remifentanil. RESULTS:Arterial remifentanil was in steady state at 12 min. One milligram IV naloxone reversed the effect of remifentanil to 93% of pre-opioid pupil-size within 4 min. The estimated duration of antagonism was 118 min. At that time, the concentration of naloxone was 0.51 ng/ml. The time course of arterial and venous serum concentrations for naloxone was similar, although arterial AUC (area under the curve) was slightly lower (94%) than the venous AUC (p = 0.03). There were no serious adverse events. CONCLUSION:Onset of reversal by IV naloxone was rapid and lasted 118 min. The minimum effective concentration was 0.5 ng/ml. Using TCI remifentanil to obtain a steady-state opioid agonism may be a useful tool to compare new naloxone products.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Tylleskar I,Skulberg AK,Skarra S,Nilsen T,Dale O

doi

10.1007/s00228-018-2545-y

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1547-1553

issue

12

eissn

0031-6970

issn

1432-1041

pii

10.1007/s00228-018-2545-y

journal_volume

74

pub_type

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