Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism

Cornett, Elyse M.; Turpin, Michelle A. Carroll; Pinner, Allison; Thakur, Pankaj; Sekaran, Tamizh Selvan Gnana; Siddaiah, Harish; Rivas, J L Merino; Yates, Anna; Huang, Genkai J.; Senthil, Anitha; Khurmi, Narjeet; Miller, Jenna; Stark, Cain W.; Urman, Richard D.; Kaye, Alan D.

doi:10.1007/s11912-020-0865-4

Cited by 21 publications

(21 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…19,20 Given the rarity of these polymorphisms, however, there are no widely accepted clinical guidelines regarding drug dose adjustments for patients with CYP3A4 polymorphisms. 5…”

Section: Cytochrome P450 3a4mentioning

confidence: 99%

“…In addition, the risk of addiction and other adverse effects from opioids has emphasized and hastened the need to incorporate precision medicine by safely and effectively delivering the right drug, at the right dose, to the right patient. 5,6 By utilizing genetic and pharmacogenomic data to inform treatment decisions in the management of pain, practitioners augment their clinical repertoire and improve patient care by minimizing toxicities and maximizing therapeutic efficacy. 1,7 The purpose of this review is to summarize the existing literature and clinical guidelines to equip clinicians to utilize genetic and pharmacogenomic data in the development of safe and effective pharmacotherapeutic regimens for the treatment of pain and opioid use disorder (OUD).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug Associations and Clinical Considerations

et al. 2021

View full text Add to dashboard Cite

Objective: To provide an overview of clinical recommendations regarding genomic medicine relating to pain management and opioid use disorder. Data Sources: A literature review was conducted using the search terms pain management, pharmacogenomics, pharmacogenetics, pharmacokinetics, pharmacodynamics, and opioids on PubMed (inception to February 1, 2021), CINAHL (2016 through February 1, 2021), and EMBASE (inception through February 1, 2021). Study Selection and Data Extraction: All relevant clinical trials, review articles, package inserts, and guidelines evaluating applicable pharmacogenotypes were considered for inclusion. Data Synthesis: More than 300 Food and Drug Administration–approved medications contain pharmacogenomic information in their labeling. Genetic variability may alter the therapeutic effects of commonly prescribed pain medications. Pharmacogenomic-guided therapy continues to gain traction in clinical practice, but a multitude of barriers to widespread pharmacogenomic implementation exist. Relevance to Patient Care and Clinical Practice: Pain is notoriously difficult to treat given the need to balance safety and efficacy when selecting pharmacotherapy. Pharmacogenomic data can help optimize outcomes for patients with pain. With improved technological advances, more affordable testing, and a better understanding of genomic variants resulting in treatment disparities, pharmacogenomics continues to gain popularity. Unfortunately, despite these and other advancements, pharmacogenomic testing and implementation remain underutilized and misunderstood in clinical care, in part because of a lack of health care professionals trained in assessing and implementing test results. Conclusions: A one-size-fits-all approach to pain management is inadequate and outdated. With increasing genomic data and pharmacogenomic understanding, patient-specific genomic testing offers a comprehensive and personalized treatment alternative worthy of additional research and consideration.

show abstract

“…19,20 Given the rarity of these polymorphisms, however, there are no widely accepted clinical guidelines regarding drug dose adjustments for patients with CYP3A4 polymorphisms. 5…”

Section: Cytochrome P450 3a4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug Associations and Clinical Considerations

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The metabolites can also be excreted by the kidneys. Pharmacokinetic studies have shown that due to the polymorphic characteristics observed in hepatic metabolism of drugs, individuals with different polymorphisms have different exposure and/or metabolism of opioid analgesics [13][14][15][16]. Some studies also show that polymorphism affected the pharmacodynamics of individuals.…”

Section: Pharmacogenetics Of Opioidsmentioning

confidence: 99%

Pharmacological Advances in Opioid Therapy: A Review of the Role of Oliceridine in Pain Management

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nonsteroidal anti-inflammatory drugs, or NSAIDs, play antipyretic, analgesic, and anti-inflammatory effects by inhibiting COX and reducing the synthesis of prostaglandins. NSAIDs are available as oral tablets and solutions [28]. Metabolism of NSAIDs is controlled by the CYP2C family of enzymes.…”

Section: Biomed Research Internationalmentioning

confidence: 99%

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Guo

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in beagles were studied. The plasma was precipitated by acetonitrile, and the two analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm); the mobile phase was acetonitrile and 0.1% formic acid with gradient mode, and the flow rate was 0.4 mL/min. In the negative ion mode, the two analytes and internal standard (IS) were monitored by multiple reaction monitoring (MRM), and the mass transition pairs were as follows: m/z 369.1→119.1 for parecoxib, m/z 313.0→118.0 for valdecoxib, and m/z 380.0→316.0 for celecoxib (IS). Six beagles were designed as a double cycle self-control experiment. In the first cycle, after intramuscular injection of parecoxib 1.33 mg/kg, 1.0 mL blood samples were collected at different times (group A). In the second cycle, the same six beagles were intravenously injected with 2 μg/kg dexmedetomidine for 7 days after one week of washing period. On day 7, after intravenous injection of 2 μg/kg dexmedetomidine for 0.5 hours, 6 beagle dogs were intramuscularly injected with 1.33 mg/kg parecoxib, and blood samples were collected at different time points (group A). The concentration of parecoxib and valdecoxib was detected by UPLC-MS/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the experimental conditions, the method has a good linear relationship for both analytes. The interday and intraday precision was less than 8.07%; the accuracy values were from -1.20% to 2.76%. Cmax of parecoxib in group A and group B was 2148.59±406.13 ng/mL and 2100.49±356.94 ng/mL, t1/2 was 0.85±0.36 h and 0.85±0.36 h, and AUC0‐t was 2429.96±323.22 ng·h/mL and 2506.38±544.83 ng·h/mL, respectively. Cmax of valdecoxib in group A and group B was 2059.15±281.86 ng/mL and 2837.39±276.78 ng/mL, t1/2 was 2.44±1.55 h and 2.91±1.27 h, and AUC0‐t was 4971.61±696.56 ng·h/mL and 6770.65±453.25 ng·h/mL, respectively. There was no significant change in the pharmacokinetics of parecoxib in groups A and B. Cmax and AUC0−∞ of valdecoxib in group A were 37.79% and 36.19% higher than those in group B, respectively, and t1/2 was increased from 2.44 h to 2.91 h. Vz/F and CLz/F were correspondingly reduced, respectively. The developed UPLC-MS/MS method for simultaneous determination of parecoxib and valdecoxib in beagle plasma was specific, accurate, rapid, and suitable for the pharmacokinetics and drug-drug interactions of parecoxib and valdecoxib. Dexmedetomidine can inhibit the metabolism of valdecoxib in beagles and increase the exposure of valdecoxib, but it does not affect the pharmacokinetics of parecoxib.

show abstract

Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism

Cited by 21 publications

References 146 publications

Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug Associations and Clinical Considerations

Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug Associations and Clinical Considerations

Pharmacological Advances in Opioid Therapy: A Review of the Role of Oliceridine in Pain Management

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Contact Info

Product

Resources

About