Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | British Journal of Clinical Pharmacology |
| Vol/bind | 67 |
| Udgave nummer | 2 |
| Sider (fra-til) | 172-9 |
| Antal sider | 7 |
| ISSN | 0306-5251 |
| DOI | |
| Status | Udgivet - 2008 |
Bibliografisk note
Keywords: Adolescent; Adult; Aged; Analgesics, Opioid; Cross-Sectional Studies; Denmark; Electrocardiography; Ether-A-Go-Go Potassium Channels; Female; Heart Conduction System; Humans; Long QT Syndrome; Male; Middle Aged; Pain; Patch-Clamp Techniques; Pharmaceutical Preparations; Torsades de Pointes; Young AdultAdgang til dokumentet
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I: British Journal of Clinical Pharmacology, Bind 67, Nr. 2, 2008, s. 172-9.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro
AU - Fanoe, Søren
AU - Jensen, Gorm Boje
AU - Sjøgren, Per
AU - Korsgaard, Mads P G
AU - Grunnet, Morten
AU - Fanoe, Søren
AU - Jensen, Gorm Boje
AU - Sjøgren, Per
AU - Korsgaard, Mads P G
AU - Grunnet, Morten
N1 - Keywords: Adolescent; Adult; Aged; Analgesics, Opioid; Cross-Sectional Studies; Denmark; Electrocardiography; Ether-A-Go-Go Potassium Channels; Female; Heart Conduction System; Humans; Long QT Syndrome; Male; Middle Aged; Pain; Patch-Clamp Techniques; Pharmaceutical Preparations; Torsades de Pointes; Young Adult
PY - 2008
Y1 - 2008
N2 - WHAT IS ALREADY KNOWN: During recent years some opioids have been associated with prolonged QT and torsade de pointes (TdP). In vitro testing has shown that most opioids can block the cardiac potassium channels. This indicates that QT prolongation and TdP could be a more general problem associated with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some opioids have been associated with prolonged QT interval and torsade de pointes (TdP). In vitro patch clamp testing has shown that most opioids can block human ether-a-go-go related gene (hERG) channels that are known to underlie cardiac repolarizing I(Kr) current. This indicates that QT prolongation and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing hERG channels. RESULTS: There were no differences in gender distribution or age between the treatment groups. The known association between methadone dose and QTc was confirmed (R(2) = 0.09; P = 0.02). Higher oxycodone dose was also associated with longer QTc (R(2) = 0.21; P = 0.02). A 100 mg higher oxycodone dose was associated with a 10 ms(1/2) (95% CI 2-19) longer QTc. Neither morphine nor tramadol dose was associated with the QTc. Electrophysiological testing revealed low-affinity inhibition of the potassium current through hERG channels expressed in HEK293 cells (IC(50) = 171 microM oxycodone). CONCLUSIONS: Among patients treated with methadone or oxycodone, higher doses were associated with longer QTc. Oxycodone is capable of inhibiting hERG channels in vitro.
AB - WHAT IS ALREADY KNOWN: During recent years some opioids have been associated with prolonged QT and torsade de pointes (TdP). In vitro testing has shown that most opioids can block the cardiac potassium channels. This indicates that QT prolongation and TdP could be a more general problem associated with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some opioids have been associated with prolonged QT interval and torsade de pointes (TdP). In vitro patch clamp testing has shown that most opioids can block human ether-a-go-go related gene (hERG) channels that are known to underlie cardiac repolarizing I(Kr) current. This indicates that QT prolongation and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing hERG channels. RESULTS: There were no differences in gender distribution or age between the treatment groups. The known association between methadone dose and QTc was confirmed (R(2) = 0.09; P = 0.02). Higher oxycodone dose was also associated with longer QTc (R(2) = 0.21; P = 0.02). A 100 mg higher oxycodone dose was associated with a 10 ms(1/2) (95% CI 2-19) longer QTc. Neither morphine nor tramadol dose was associated with the QTc. Electrophysiological testing revealed low-affinity inhibition of the potassium current through hERG channels expressed in HEK293 cells (IC(50) = 171 microM oxycodone). CONCLUSIONS: Among patients treated with methadone or oxycodone, higher doses were associated with longer QTc. Oxycodone is capable of inhibiting hERG channels in vitro.
U2 - 10.1111/j.1365-2125.2008.03327.x
DO - 10.1111/j.1365-2125.2008.03327.x
M3 - Journal article
C2 - 19159406
SN - 0306-5251
VL - 67
SP - 172
EP - 179
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 2
ER -