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.

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

“…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 .…”

“…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 .…”

Theophylline: a review of population pharmacokinetic analyses

“…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.…”

“…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.…”

“…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.…”