Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/95249
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Li, Y. | - |
dc.contributor.author | Jackson, K. | - |
dc.contributor.author | Slon, B. | - |
dc.contributor.author | Hardy, J. | - |
dc.contributor.author | Franco, M. | - |
dc.contributor.author | William, L. | - |
dc.contributor.author | Poon, P. | - |
dc.contributor.author | Coller, J. | - |
dc.contributor.author | Hutchinson, M. | - |
dc.contributor.author | Currow, D. | - |
dc.contributor.author | Somogyi, A. | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | British Journal of Clinical Pharmacology, 2015; 80(2):276-284 | - |
dc.identifier.issn | 0306-5251 | - |
dc.identifier.issn | 1365-2125 | - |
dc.identifier.uri | http://hdl.handle.net/2440/95249 | - |
dc.description.abstract | AIMS: Ketamine analgesia is limited by low intrinsic efficacy compounded by large interindividual variability in drug responses, possibly due to the heterogeneity in drug concentration. The CYP2B6*6 allele is associated with substantially reduced ketamine metabolism in vitro and, therefore, may affect ketamine clearance. Our aims were to examine the impact of the CYP2B6*6 allele on ketamine plasma clearance and on adverse effects in chronic pain patients. METHODS: CYP2B6 genotypes were identified in 49 chronic pain patients who received 24 h continuous subcutaneous infusions of ketamine. Steady-state plasma concentrations of ketamine (Css,k ) and norketamine (Css,nk ) were determined using HPLC. RESULTS: The median plasma clearance of ketamine after 100 mg 24 h(-1) dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h(-1) ) and CYP2B6*1/*6 (40.6 l h(-1) ) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h(-1) , P < 0.001). The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Patients who experienced adverse effects had lower plasma clearance (45.6 l h(-1) ) than those who did not (52.6 l h(-1) , P = 0.04). The CYP2B6*6 genotype and age, and their combined impact explained 40%, 30% and 60% of the variation in Css,k , respectively. Similar results were observed after higher doses. CONCLUSIONS: The CYP2B6*6 allele is associated with a substantial decrease in steady-state ketamine plasma clearance in chronic pain patients. The decreased clearance and resultant higher plasma concentrations may be associated with a higher incidence of ketamine adverse effects. | - |
dc.description.statementofresponsibility | Yibai Li, Kate A. Jackson, Barry Slon, Janet R. Hardy, Michael Franco, Leeroy William, Peter Poon, Janet K. Coller, Mark R. Hutchinson, David C. Currow, and Andrew A. Somogyi | - |
dc.language.iso | en | - |
dc.publisher | Wiley | - |
dc.rights | © 2015 The British Pharmacological Society | - |
dc.source.uri | http://dx.doi.org/10.1111/bcp.12614 | - |
dc.subject | adverse effects | - |
dc.subject | age factors | - |
dc.subject | cytochrome P-450 CYP2B6 | - |
dc.subject | ketamine | - |
dc.subject | metabolic clearance rate | - |
dc.subject | polymorphism | - |
dc.title | CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1111/bcp.12614 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/DP110100297 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Coller, J. [0000-0002-8273-5048] | - |
dc.identifier.orcid | Hutchinson, M. [0000-0003-2154-5950] | - |
dc.identifier.orcid | Somogyi, A. [0000-0003-4779-0380] | - |
Appears in Collections: | Aurora harvest 7 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.