Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Clin Pharmacol
2009 Feb 01;672:172-9. doi: 10.1111/j.1365-2125.2008.03327.x.
Show Gene links
Show Anatomy links
Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro.
Fanoe S
,
Jensen GB
,
Sjøgren P
,
Korsgaard MP
,
Grunnet M
.
???displayArticle.abstract???
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. 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. 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. 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. 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). Among patients treated with methadone or oxycodone, higher doses were associated with longer QTc. Oxycodone is capable of inhibiting hERG channels in vitro.
Al-Shakarshi,
[Life-threatening, recurrent arrhythmia in patients on high-dose methadone treatment: torsade de pointes].
2004, Pubmed
Al-Shakarshi,
[Life-threatening, recurrent arrhythmia in patients on high-dose methadone treatment: torsade de pointes].
2004,
Pubmed
Bland,
Statistical methods for assessing agreement between two methods of clinical measurement.
1986,
Pubmed
Cone,
Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions.
2004,
Pubmed
D'Aunno,
Changes in methadone treatment practices: results from a national panel study, 1988-2000.
2002,
Pubmed
Ehret,
Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors.
2006,
Pubmed
Eriksen,
Epidemiology of chronic non-malignant pain in Denmark.
2003,
Pubmed
Eriksen,
Critical issues on opioids in chronic non-cancer pain: an epidemiological study.
2006,
Pubmed
Fanoe,
Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen.
2007,
Pubmed
Franz,
Cycle length dependence of human action potential duration in vivo. Effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies.
1988,
Pubmed
Goldenberg,
QT interval: how to measure it and what is "normal".
2006,
Pubmed
Grunnet,
Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels.
2001,
Pubmed
,
Xenbase
Jespersen,
Dual-function vector for protein expression in both mammalian cells and Xenopus laevis oocytes.
2002,
Pubmed
,
Xenbase
Jung,
Interpretation of opioid levels: comparison of levels during chronic pain therapy to levels from forensic autopsies.
2005,
Pubmed
Justo,
Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients.
2006,
Pubmed
Katchman,
Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents.
2002,
Pubmed
Kornick,
QTc interval prolongation associated with intravenous methadone.
2003,
Pubmed
Krantz,
Torsade de pointes associated with very-high-dose methadone.
2002,
Pubmed
Laguna,
New algorithm for QT interval analysis in 24-hour Holter ECG: performance and applications.
1990,
Pubmed
Leavitt,
When "enough" is not enough: new perspectives on optimal methadone maintenance dose.
2000,
Pubmed
Martell,
The impact of methadone induction on cardiac conduction in opiate users.
2003,
Pubmed
Mathes,
QPatch: the past, present and future of automated patch clamp.
2006,
Pubmed
NULL,
World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects.
1997,
Pubmed
Paulozzi,
Opioid analgesics and rates of fatal drug poisoning in the United States.
2006,
Pubmed
Pereira,
Equianalgesic dose ratios for opioids. a critical review and proposals for long-term dosing.
2001,
Pubmed
Redfern,
Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development.
2003,
Pubmed
Roden,
Drug-induced prolongation of the QT interval.
2004,
Pubmed
Sanguinetti,
Predicting drug-hERG channel interactions that cause acquired long QT syndrome.
2005,
Pubmed
Shah,
Refining detection of drug-induced proarrhythmia: QT interval and TRIaD.
2005,
Pubmed