The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Stereoselective Block of hERG Channel by (S)-Methadone and QT Interval Prolongation in CYP2B6 Slow Metabolizers
Open accessAbstract
Methadone inhibits the cardiac potassium channel hERG and can cause a prolonged QT interval. Methadone is chiral but its therapeutic activity is mainly due to (R)-methadone. Whole-cell patch-clamp experiments using cells expressing hERG showed that (S)-methadone blocked the hERG current 3.5-fold more potently than (R)-methadone (IC50s (half-maximal inhibitory concentrations) at 37 degrees C: 2 and 7 microM). As CYP2B6 slow metabolizer (SM) status results in a reduced ability to metabolize (S)-methadone, electrocardiograms, CYP2B6 genotypes, and (R)- and (S)-methadone plasma concentrations were obtained for 179 patients receiving (R,S)-methadone. The mean heart-rate-corrected QT (QTc) was higher in CYP2B6 SMs (*6/*6 genotype; 439+/-25 ms; n=11) than in extensive metabolizers (non *6/*6; 421+/-25 ms; n=168; P=0.017). CYP2B6 SM status was associated with an increased risk of prolonged QTc (odds ratio=4.5, 95% confidence interval=1.2-17.7; P=0.03). This study reports the first genetic factor implicated in methadone metabolism that may increase the risk of cardiac arrhythmias and sudden death. This risk could be reduced by the administration of (R)-methadone.
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Sanguinetti, M. C., Jiang, C., Curran, M. E., & Keating, M. T. (1995) · Cell · doi:10.1016/0092-8674(95)90340-2 · Cited by 2,423
Eap, C. B., Buclin, T., & Baumann, P. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241140-00003 · Cited by 599
Self-citationLang, T., Klein, K., Fischer, J., Nussler, A. K., Neuhaus, P., Hofmann, U., Eichelbaum, M., Schwab, M. G., & Zanger, U. M. (2001) · Pharmacogenetics · doi:10.1097/00008571-200107000-00004 · Cited by 571
Torsade de Pointes Associated with Very-High-Dose Methadone
Krantz, M. J., Lewkowiez, L., Hays, H., Woodroffe, M. A., Robertson, A. D., & Mehler, P. S. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-6-200209170-00010 · Cited by 426
Laurel Gorman, A., Elliott, K. J., & Inturrisi, C. E. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)13391-2 · Cited by 398
Codd, E. E., Shank, R. P., Schupsky, J. J., & Raffa, R. B. (1995) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10630-7 · Cited by 388
Predicting drug–hERG channel interactions that cause acquired long QT syndrome
Sanguinetti, M. C., & Mitcheson, J. S. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.01.003 · Cited by 300
Klein, K., Lang, T., Saussele, T., Barbosa-Sicard, E., Schunck, W.-H., Eichelbaum, M., Schwab, M., & Zanger, U. M. (2005) · Pharmacogenetics and Genomics · doi:10.1097/01213011-200512000-00004 · Cited by 269
Influence of Opioid Agonists on Cardiac Human Ether-a-go-go-related Gene K+ Currents
Katchman, A. N., McGroary, K. A., Kilborn, M. J., Kornick, C. A., Manfredi, P. L., Woosley, R. L., & Ebert, S. N. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.038240 · Cited by 264
Ebert, B., Andersen, S., & Krogsgaard-Larsen, P. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11364-3 · Cited by 255
Cited by
Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation
Zanger, U. M., Turpeinen, M., Klein, K., & Schwab, M. (2008) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-008-2291-6 · Cited by 593
Zanger, U. M., & Klein, K. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00024 · Cited by 345
QT Interval Screening in Methadone Maintenance Treatment: Report of a SAMHSA Expert Panel
Martin, J. A., Campbell, A., Killip, T., Kotz, M., Krantz, M. J., Kreek, M. J., McCarroll, B. A., Mehta, D., Payte, J. T., Stimmel, B., et al. (2011) · Journal of Addictive Diseases · doi:10.1080/10550887.2011.610710 · Cited by 87
“52 , 53 It may be that slow metabolizers of CYP 2B6 who possess a *6/*6 genotype have difficulty metabolizing S -methadone but not R -methadone.”
Background
Metadata
- Authors
- Eap, C. B., Crettol, S., Rougier, J.-S., Schläpfer, J., Sintra Grilo, L., Déglon, J.-J., Besson, J., Croquette-Krokar, M., Carrupt, P.-A., & Abriel, H.
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2007-02-28
- Volume
- 81
- Issue
- 5
- Pages
- 719-728
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2140003901
- Cited by
- 255
- References
- 32
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- green
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- Eap, C. B., Crettol, S., Rougier, J.-S., Schläpfer, J., Sintra Grilo, L., Déglon, J.-J., Besson, J., Croquette-Krokar, M., Carrupt, P.-A., & Abriel, H. (2007). Stereoselective Block of hERG Channel by (S)-Methadone and QT Interval Prolongation in CYP2B6 Slow Metabolizers. Clinical Pharmacology & Therapeutics. https://doi.org/10.1038/sj.clpt.6100120
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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