Associations between CYP2E1 promoter polymorphisms and plasma 1,3-dimethyluric acid/theophylline ratios

Yoon, Yeomin; Park, Hyung-Doo; Park, Kyoung Un; Kim, Jin Q; Chang, Yoon-Seok; Song, Junghan

doi:10.1007/s00228-006-0165-4

Cited by 12 publications

(14 citation statements)

References 14 publications

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“…Indeed, Yoon et al . observed that 8‐hydroxylation of theophylline (primary metabolic pathway) was significantly affected by genetic polymorphism in CYP2E1 . The results from in vitro studies suggest that CYP2E1 may play an important role in 8‐hydroxylation of theophylline in human beings .…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, to fully understand the factors that affect the metabolism of theophylline is extremely important for clinicians. Although several CYP450 isoenzymes, such as CYP1A2, CYP1A1 and CYP2E1, have been demonstrated to catalyse the metabolism of theophylline in human beings , theophylline is mainly metabolized by cytochrome P450 1A2 (CYP1A2) (approximately 80%) . Both in vivo and in vitro studies have confirmed that CYP1A2 plays a major role in theophylline metabolism at pharmacological concentrations by both N‐demethylation and 8‐hydroxylation .…”

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confidence: 99%

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Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

Wang

Deng

et al. 2012

Basic Clin Pharma Tox

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This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese population. Four polymorphisms CYP1A2*1C (G-3860A), G-3113A, CYP1A2*1F (C-163A) and CYP1A2*1B (C-5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200-mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17X/137X) after administration of 100-mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high-performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the -3113 AA genotype compared with those with the -3113 AG genotype (0.35 AE 0.04 versus 0.48 AE 0.07, p = 0.016) or the -3113 GG genotype (0.35 AE 0.04 versus 0.58 AE 0.22, p = 0.037). CYP1A2*1F polymorphisms were associated with increased CYP1A2 activity in volunteers with -3860G/-3113G/5347C homozygosity (0.66 AE 0.24 versus 0.46 AE 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.Theophylline has been used in the treatment of asthma patients for many years on the basis of its ability to suppress late asthma reactions in antigen challenge tests [1,2] and to alleviate airway hyper-responsiveness [3]. However, the agent has a narrow therapeutic range (5-20 lg/mL) and excessively high blood concentrations of theophylline, which has caused life-threatening toxicity in the clinic [4]. Therefore, to fully understand the factors that affect the metabolism of theophylline is extremely important for clinicians. Although several CYP450 isoenzymes, such as CYP1A2, CYP1A1 and CYP2E1, have been demonstrated to catalyse the metabolism of theophylline in human beings [5][6][7], theophylline is mainly metabolized by cytochrome P450 1A2 (CYP1A2) (approximately 80%) [8]. Both in vivo and in vitro studies have confirmed that CYP1A2 plays a major role in theophylline metabolism at pharmacological concentrations by both N-demethylation and 8-hydroxylation [7,9]. Thus, its metabolism may be influenced by CYP1A2 polymorphisms.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

Wang

Deng

et al. 2012

Basic Clin Pharma Tox

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“…In adults, 90% of theophylline is metabolized by liver cytochrome P450 (CYP450) 1A2, and in neonates, approximately 50% is excreted unchanged in the urine because of their immature hepatic function . Many factors are reported to affect CYP1A2 activity, such as single nucleotide polymorphisms of CYP1A2 and concurrent administration of drugs including phenytoin, phenobarbitone, erythromycin and quinolone antibiotics . Therefore, variability in theophylline clearance may be explained in part by these factors.…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…8 Many factors are reported to affect CYP1A2 activity, such as single nucleotide polymorphisms of CYP1A2 and concurrent administration of drugs including phenytoin, phenobarbitone, erythromycin and quinolone antibiotics. 1,9,10 Therefore, variability in theophylline clearance may be explained in part by these factors. The elimination half-life of theophylline was 3Á5 h in paediatric patients and 5-6 h in adults, and it was prolonged in the elderly.…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…In fact, several studies have reported the relationship between the pharmacokinetics of theophylline and the genotypes of the CYP1A2 gene. 9,10,51,52 For example, CYP 1A2*1C (À3860G>A) and CYP1A2*1F (À163C>A) have been reported to affect the low and high inducibility of CYP1A2 in smokers, 53,54 respectively. Unfortunately, none of the studies included in this review explored the effects of gene polymorphisms on the disposition of theophylline in adults.…”

Section: Population Pharmacokinetic Analysis Of Theophylline In Adultsmentioning

confidence: 99%

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Theophylline: a review of population pharmacokinetic analyses

Jiang

Meng

et al. 2016

J Clin Pharm Ther

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This review concludes that body weight and age were the most important factors associated with the clearance of theophylline in paediatric patients. Body weight, age and smoking were most frequently used to estimate the clearance of theophylline in adults. Future studies are warranted to detect the influence of new factors, such as cytochrome P450 (CYP) 1A2 gene polymorphisms, on the pharmacokinetics of theophylline because some pharmacokinetic variability was not fully explained.

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Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes

Dolžan

2012

Pharmacogenetics and Individualized Therapy

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Associations between CYP2E1 promoter polymorphisms and plasma 1,3-dimethyluric acid/theophylline ratios

Abstract: We confirm that hydroxylation at the 8 position of theophylline (1,3-DMU) is significantly affected by genetic polymorphism in CYP2E1 in addition to CYP1A2.

Cited by 12 publications

References 14 publications

Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

Theophylline: a review of population pharmacokinetic analyses

Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes

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