Tags

Type your tag names separated by a space and hit enter

Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro.
Br J Clin Pharmacol. 2009 Feb; 67(2):172-9.BJ

Abstract

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.

Authors+Show Affiliations

Department of Cardiology, Copenhagen University Hospital Hvidovre, Kettegård Allé 30, Hvidovre, Denmark. sfanoe@dadlnet.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19159406

Citation

Fanoe, Søren, et al. "Oxycodone Is Associated With Dose-dependent QTc Prolongation in Patients and Low-affinity Inhibiting of hERG Activity in Vitro." British Journal of Clinical Pharmacology, vol. 67, no. 2, 2009, pp. 172-9.
Fanoe S, Jensen GB, Sjøgren P, et al. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro. Br J Clin Pharmacol. 2009;67(2):172-9.
Fanoe, S., Jensen, G. B., Sjøgren, P., Korsgaard, M. P., & Grunnet, M. (2009). Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro. British Journal of Clinical Pharmacology, 67(2), 172-9. https://doi.org/10.1111/j.1365-2125.2008.03327.x
Fanoe S, et al. Oxycodone Is Associated With Dose-dependent QTc Prolongation in Patients and Low-affinity Inhibiting of hERG Activity in Vitro. Br J Clin Pharmacol. 2009;67(2):172-9. PubMed PMID: 19159406.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2008/10/15/ PY - 2009/1/23/entrez PY - 2009/1/23/pubmed PY - 2009/9/11/medline SP - 172 EP - 9 JF - British journal of clinical pharmacology JO - Br J Clin Pharmacol VL - 67 IS - 2 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. SN - 1365-2125 UR - https://www.unboundmedicine.com/medline/citation/19159406/Oxycodone_is_associated_with_dose_dependent_QTc_prolongation_in_patients_and_low_affinity_inhibiting_of_hERG_activity_in_vitro_ L2 - https://doi.org/10.1111/j.1365-2125.2008.03327.x DB - PRIME DP - Unbound Medicine ER -