Cytochrome P4502C9 activity in end‐stage renal disease

Dreisbach, Albert W.; Japa, Shanker; Gebrekal, A.B.; Mowry, Sarah E.; Lertora, Juan J.L.; Kamath, Burde L.; Rettie, Allan E.

doi:10.1016/s0009-9236(03)00015-8

Cited by 94 publications

(62 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, in a small subsample of patients for whom serum albumin data was available, we found no between-group difference 7 for example, increased circulating uremic factors, increased cytokines, and decreased cytochrome P450 metabolism. 18 We did not investigate these possibilities. However, in another study, we found that warfarin-treated patients who experienced an episode of in-hospital acute kidney injury (AKI) exhibited INR-dependent responses.…”

Section: Limitationsmentioning

confidence: 99%

Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist-Managed Anticoagulation Clinic

Kleinow¹,

Garwood²,

Clemente³

et al. 2011

JMCP

View full text Add to dashboard Cite

Section: Limitationsmentioning

confidence: 99%

Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist-Managed Anticoagulation Clinic

Kleinow¹,

Garwood²,

Clemente³

et al. 2011

JMCP

View full text Add to dashboard Cite

“…CYP2C9 is the principal enzyme that metabolizes the pharmacologically active S-warfarin. In patients with end-stage renal disease, there is a 50% increase in the plasma warfarin S/R ratio relative to control subjects, reflecting reduced activity of CYP2C9 (Dreisbach et al, 2003). Consistent with this observation is the finding that compared with patients with normal or mildly impaired renal function patients with moderate impairment have been reported to require 7.2%-10.9% lower dose, and patients with severe impairment required 13.9%-21.3% lower dose, of warfarin (Limdi et al, 2010).…”

Section: Evidence For Potential Phenoconversion Of Dmes In Other Inflmentioning

confidence: 99%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

View full text Add to dashboard Cite

Phenoconversion transiently converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs) of drugs, potentially with corresponding changes in clinical response. This phenomenon, typically resulting from coadministration of medications that inhibit certain drug metabolizing enzymes (DMEs), is especially well documented for enzymes of the cytochrome P450 family. Nonclinical evidence gathered over the last two decades also strongly implicates elevated levels of some proinflammatory cytokines, released during inflammation, in down-regulation of drug metabolism, especially by certain DMEs of the P450 family, thereby potentially causing transient phenoconversion. Clinically, phenoconversion of NAT2, CYP2C19, and CYP2D6 has been documented in inflammatory conditions associated with elevated cytokines, such as human immunodeficiency virus infection, cancer, and liver disease. The potential of other inflammatory conditions to cause phenoconversion has not been studied but experimental and anecdotal clinical evidence supports infectioninduced down-regulation of CYP1A2, CYP3A4, and CYP2C9 as well. Collectively, the evidence supports a hypothesis that certain inflammatory conditions associated with elevated proinflammatory cytokines may cause phenoconversion of certain DMEs. Since inflammatory conditions associated with elevated levels of proinflammatory cytokines are highly prevalent, phenoconversion of genotypic EM patients into transient phenotypic PMs may be more frequent than appreciated. Since drug pharmacokinetics, and therefore the clinical response, is influenced by DME phenotype rather than genotype per se, phenoconversion (whatever its cause) can have a significant impact on the analysis and interpretation of genotype-focused clinical outcome association studies. There is a risk that focusing on genotype alone may miss important associations between clinical outcomes and DME phenotypes, thus compromising future prospects of personalized medicine.

show abstract

“…Leblond et al 111,112 reported a reduction in CYP2C11, 3A1, and 3A2 expression, on both the gene and protein levels, in CRF rats, and it was associated with a reduction in erythromycin and aminopyrine metabolism. In addition, in CKD patients, mitigation of CYPmediated drug metabolism is shown, 113,114 including changes in bupropion, alprazolam, and fexofenadine pharmacokinetics. [115][116][117] Moreover, is has been shown both in vitro and in vivo that hemodialysis improves functional expression of hepatic CYP3A4, 118,119 implicating a role for uremic toxins in altering drug metabolism in CKD patients.…”

Section: Intracellular Fate Of Uremic Toxinsmentioning

confidence: 99%

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

Masereeuw

Mutsaers

Toyohara³

et al. 2014

Seminars in Nephrology

134

122

View full text Add to dashboard Cite

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.

show abstract

Cytochrome P4502C9 activity in end‐stage renal disease

Cited by 94 publications

References 7 publications

Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist-Managed Anticoagulation Clinic

Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist-Managed Anticoagulation Clinic

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

Contact Info

Product

Resources

About