Pharmacogenetics in perioperative medicine

Cohen, Mindy; Sadhasivam, Senthilkumar; Vinks, Alexander A.

doi:10.1097/aco.0b013e3283556129

Cited by 58 publications

(22 citation statements)

References 77 publications

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“…In an age where personalized medicine is gaining more popularity, there is increasing focus to better understand the pharmacogenetic influence on the response and side effects of opioid medications [27][28][29][30]. To this end, the main purpose of this study was to identify the role of pharmacogenetic variability on the pharmacokinetics of oral oxycodone in children undergoing surgery.…”

Section: Discussionmentioning

confidence: 99%

CYP2D6 Pharmacogenetic and Oxycodone Pharmacokinetic Association Study in Pediatric Surgical Patients

et al. 2017

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Section: Discussionmentioning

confidence: 99%

CYP2D6 Pharmacogenetic and Oxycodone Pharmacokinetic Association Study in Pediatric Surgical Patients

et al. 2017

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“…Sample size. The primary outcome was the frequency of the ABCB1 rs1045642 [15,30] variant among DOA and LOA. The frequency in the general population, as estimated from HapMap, was used as a proxy for the frequency in the LOA population.…”

Section: Discussionmentioning

confidence: 99%

The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction

Christoffersen

Damkier

Feddersen

et al. 2016

Basic Clin Pharma Tox

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Sudden death due to acute intoxication occurs frequently in patients with opioid addiction (OA). To examine whether certain genotypes were associated with this, we examined the frequencies of 29 SNPs located in candidate genes related to opioid pharmacology: ABCB1, OPRM1, UGT2B7, CYP3A5, CYP2B6, CYP2C19, CYP2D6, COMT, KCNJ6 and SCN9A in 274 deceased patients with OA (DOA), 309 living patients with OA (LOA) and in 394 healthy volunteers (HV). The main hypothesis of the study was that subjects homozygous for the variant 3435T in ABCB1 (rs1045642) occur more frequently in DOA than in LOA and HV because morphine and methadone more readily cross the blood barrier in these subjects due to a lower efflux transporter activity of the ABCB1 (p-glycoprotein) transporter. Our results did not support this hypothesis, because no statistically significant difference (p = 0.506) in the frequency of the TT genotype of rs1045642 was observed between the DOA, LOA and HV cohorts. However, for another ABCB1 variant, rs9282564, we found that the frequencies of the AG and TT genotypes were 13, 21 and 25% in DOA, LOA and HV, respectively, and after correcting for age, sex and multiple testing, the differences between DOA and LOA were statistically significantly different (p = 0.027). The COMT rs4680 AA genotype frequencies were 25%, 35% and 31% in DOA, LOA and HV, respectively, and the difference between DOA and LOA was also statistically significant (p = 0.0028). In conclusion, this study generated two hypotheses suggesting possible associations of a reduced risk of death and carrying, respectively, the ABCB1 rs9282564 AG and TT genotypes and the COMT rs4680 AA genotype among patients with OA. These findings should be confirmed in independent cohorts, and if a causal relationship between these variants and fatal poisoning in OA is confirmed, then it may be possible at least in theory to personalize prevention of sudden death in this patient group.

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“…The role of pharmacogenomics continues to be investigated and a number of excellent reviews are available [75][76][77][78][79]. While each isolated pharmacogenomics influence may be discerned, the complex interplay of all these influences in any one individual makes clinical interpretation difficult.…”

Section: Pharmacogenomicsmentioning

confidence: 99%

Considerations when using pharmacokinetic/pharmacodynamic modeling to determine the effectiveness of simple analgesics in children

Anderson

Hannam

2015

Expert Opinion on Drug Metabolism & Toxicology

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Nonlinear mixed effects models help interpret analgesic data and their use is increasing. The PK is relatively well understood. The next investigative step will involve investigation into covariate effects for PD. Mathematical functions for both placebo models and dropout models are well described and should be incorporated into analgesic effectiveness studies that investigate a range of doses. Improvements in pain assessment tools and a greater understanding of pharmacogenomics factors will help individualize analgesic therapy.

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Pharmacogenetics in perioperative medicine

Abstract: In the near future, pharmacogenetic approaches may facilitate personalized perioperative intervention trials.

Cited by 58 publications

References 77 publications

CYP2D6 Pharmacogenetic and Oxycodone Pharmacokinetic Association Study in Pediatric Surgical Patients

CYP2D6 Pharmacogenetic and Oxycodone Pharmacokinetic Association Study in Pediatric Surgical Patients

The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction

Considerations when using pharmacokinetic/pharmacodynamic modeling to determine the effectiveness of simple analgesics in children

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