Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis

Kaneshiro, Yasunori; Oda, Yutaka; Iwakiri, Kentaro; Masada, Toshiaki; Iwaki, Hiroaki; Hirota, Yoshio; Kondo, Kyoko; Takaoka, Kunio

doi:10.1016/j.clpt.2006.07.004

Cited by 36 publications

(27 citation statements)

References 26 publications

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“…More recently, low hepatic CYP3A activity was found to be associated with the risk for corticosteroid-induced osteonecrosis (Kaneshiro et al, 2006). Our finding that CYP3A5 polymorphism may influence basal levels of hepatic CYP3A activity and the inductive effects of corticosteroids suggests that absence of CYP3A5*1 alleles may be associated with risk for corticosteroid-induced osteonecrosis.…”

Section: Discussionmentioning

confidence: 57%

The Influence of CYP3A5 Genotype on Dexamethasone Induction of CYP3A Activity in African Americans

Roberts¹,

Rollins²,

Kashuba³

et al. 2008

Drug Metab Dispos

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ABSTRACT:The CYP3A5*1 allele has been associated with differences in the metabolism of some CYP3A substrates. CYP3A5 polymorphism may also influence susceptibility for certain drug interactions. We have previously noted a correlation between basal CYP3A activity and the inductive effects of dexamethasone using the erythromycin breath test (ERBT). To determine whether CYP3A5 polymorphism influences induction of CYP3A activity, we examined the effect of an antiemetic regimen of dexamethasone, and the prototypical inducer rifampin, on the ERBT in African American volunteers prospectively stratified by CYP3A5*1 allele carrier status.Mean basal ERBTs were significantly higher in CYP3A5*1 carriers (2.71 ؎ 0.53%) versus noncarriers (2.12 ؎ 0.37%, P ‫؍‬ 0.006). Rifampin increased ERBTs in CYP3A5*1 carriers (4.68 versus 2.60%, P ‫؍‬ 0.0008) and noncarriers (3.55 versus 2.11%, P ‫؍‬ 0.0017), whereas dexamethasone increased ERBTs only in CYP3A5*1 noncarriers (3.03 versus 2.14%, P ‫؍‬ 0.031). CYP3A5 polymorphism appears to influence susceptibility to induction-type drug interactions for some inducers, and CYP3A5*1 noncarriers may be more susceptible to the inductive effects of dexamethasone as a result of lower basal CYP3A activity.Members of the cytochrome P450 3A (CYP3A) subfamily of drug-metabolizing enzymes are the most abundantly expressed cytochrome P450 enzymes in human liver and are involved in the metabolism of nearly 50% of clinically used drugs (Wilkinson, 2005). In adults, hepatic CYP3A activity reflects primarily the net contributions of CYP3A4 and CYP3A5, which share overlapping substrate specificities but differ with regard to tissue expression and transcriptional regulation (Gibson et al., 2002;Goodwin et al., 2002;. Recent efforts to understand interindividual variability in CYP3A activity have focused primarily on CYP3A5 polymorphisms because variability in the contribution of functional CYP3A5 activity could influence an individual's susceptibility to inducer-or inhibitor-mediated drug interactions. The major CYP3A5 polymorphisms include the CYP3A5*3, *6, and *7 alleles, which are functionally inactive because of single nucleotide polymorphisms that result in either splice defects or the introduction of an early stop codon that results in reduced production of the full-length active protein Wojnowski, 2004;Xie et al., 2004). CYP3A5*1 is the only functional CYP3A5 allele known to contribute to total CYP3A activity, and the frequency of the CYP3A5*1 allele has been shown to differ among ethnic groups (Kuehl et al., 2001). The CYP3A5*1 allele has been associated with higher midazolam systemic clearance and tacrolimus dose requirements (Kuehl et al., 2001;Wong et al., 2004) and greater metabolism of quinidine and saquinavir (Mouly et al., 2005;Mirghani et al., 2006).Less is known about the influence of the CYP3A5*1 allele on susceptibility for drug interactions caused by different CYP3A inducers and inhibitors. Recently, the CYP3A5*1 allele was shown to influence susceptibility to the inhibitory effects of fl...

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Section: Discussionmentioning

confidence: 57%

The Influence of CYP3A5 Genotype on Dexamethasone Induction of CYP3A Activity in African Americans

Roberts¹,

Rollins²,

Kashuba³

et al. 2008

Drug Metab Dispos

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“…The bispectral index (BIS) is a processed electroencephalogram (EEG) and a reliable parameter for indicating the depth of anesthesia as well as the levels of sedation used to maintain this depth of anesthesia [2,3]. Although the pharmacokinetics of midazolam has been extensively studied [4][5][6][7][8], little is known about the electroencephalographic effects of higher doses of midazolam used for the induction of general anesthesia relative to those used for sedation [9], and their relationships with plasma and effect site concentrations. We have measured the plasma concentrations of midazolam following bolus administration of two different doses, simulated the effect-site concentrations, and examined the relationships between electroencephalographic parameters, such as BIS, relative beta ratio, and 95% spectral edge frequency (SEF95).…”

Section: Introductionmentioning

confidence: 99%

Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations

et al. 2010

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“…It is therefore assumed that genetic variability in metabolizing agents (CYP and UGT family) and drug transporters (ABC family) might be crucial. Some authors showed an association between high risk of steroid induced AVN and low activity of CYP enzymes, especially CYP3A (83,84). These fi ndings were also considered in additional studies.…”

Section: Genetic Polymorphisms Involved In Dna Oxidation Injury In Bomentioning

confidence: 94%

“…These fi ndings were also considered in additional studies. SNPs analysis of the CYP3A4, CYP2D6 and CYP2C19 revealed the association with AVN development (21, [83][84][85]. Different distribution between AVN patients and controls showed 4 SNPs of the CYP2C8 gene and only rs1934951 in this gene was signifi cantly associated with AVN development (86).…”

Section: Genetic Polymorphisms Involved In Dna Oxidation Injury In Bomentioning

confidence: 97%

Avascular necrosis of bone in childhood cancer patients: a possible role of genetic susceptibility

Geczova¹,

Šoltýsová²,

Gécz³

et al. 2015

BLL

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Abstract:With the increasing number of paediatric cancer patients and with their prolonged survival, the evidence of a number of serious complications induced by anticancer therapy is rising. Osteonecrosis (ON) of bone is one of these treatment-related effects with a multifactorial pathogenesis. In the past few years, several polymorphisms of candidate genes with possible role in development of this disorder were studied. We summarized potential risk factors leading to increased susceptibility to osteonecrosis of bone development in cancer patients during childhood and to present current knowledge in the fi eld of genetic aspects of this condition (Ref. 86). Text in PDF www.elis.sk.

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Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis

Abstract: Low hepatic CYP3A activity may significantly contribute to the risk for steroid-induced ONFH.

Cited by 36 publications

References 26 publications

The Influence of CYP3A5 Genotype on Dexamethasone Induction of CYP3A Activity in African Americans

The Influence of CYP3A5 Genotype on Dexamethasone Induction of CYP3A Activity in African Americans

Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations

Avascular necrosis of bone in childhood cancer patients: a possible role of genetic susceptibility

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