Disease relevance of Ba 2751

• Inhibition of 1,3-dimethyluric acid formation, which is catalyzed by CYP1A2 and CYP2E1, progressively decreased from 58% in healthy subjects to 43% and 7% in patients with mild cirrhosis and those with severe cirrhosis, respectively [1].
• Hence, it was expected that the formation of 1,3-dimethyluric acid would show an increase in rats with renal failure as a result of induction of CYP2E1 [2].
• Pharmacokinetics of theophylline in diabetes mellitus rats: induction of CYP1A2 and CYP2E1 on 1,3-dimethyluric acid formation [3].
• RESULTS: Acute hypoxia did not alter the pharmacokinetics of theophylline [half-life+/-SD: 9.29+/-1.77 versus 9.39+/-1.40 (hypoxia)], 1,3-dimethyluric acid (12.9+/-4.72 versus 15.1+/-8.59), verapamil (2.00+/-0.98 versus 1.79+/-0.58), or norverapamil (7.98+/-2.94 versus 9.91+/-6.40) [4].
• The pharmacokinetics of theophylline and its metabolites, caffeine, 1,3-dimethyluric acid, 1-methyluric acid and 3-methylxanthine were studied in a 5-day old 1.3 kg premature neonate who accidentally received 180 mg theophylline in 26 h during treatment for bradycardia [5].

High impact information on Ba 2751

• The demethylation pathway occurring predominantly in adults was substituted by N-methylation to caffeine in premature infants; the other major metabolic pathway of theophylline in adults, C-8 oxidation to 1,3-dimethyluric acid, was slightly diminished [6].
• Increase in apparent theophylline concentration in the serum of two patients as measured by some immunoassay methods (caused by 1,3-dimethyluric acid?) [7].
• Compared with H(CONT) in H(INFLA) the production of theophylline metabolites, 3-methylxanthine (3MX), 1-methyluric acid (1MU), and 1,3-dimethyluric acid (1,3DMU) was reduced as was the amount of total P450, while lipid peroxidation was increased [8].
• Plasma concentrations of theophylline, and urinary recovery of theophylline and its metabolites [1, 3-dimethyluric acid, 3-methyl xanthine and 1-methyluric acid] were measured before and after highly purified subunit influenza vaccination in seven healthy subjects, and five subjects with chronic obstructive bronchitis [9].
• The concentrations of theophylline, 1,3-dimethyluric acid, verapamil, and norverapamil were determined in serial blood samples by means of liquid chromatography-mass spectrometry (LC/MS/MS) [4].

Chemical compound and disease context of Ba 2751

• The results led us to conclude that in rats with uranyl nitrate-induced renal failure after the administration of aminophylline, 5 mg kg(-1) as theophylline, there was an increase in the formation of 1,3-dimethyluric acid as a result of an increase in CYP2E1 expression [2].

Biological context of Ba 2751

• In the ST-pretreated group, plasma concentration (Cp), the area under Cp-time profile (AUC) and urinary excretion of TP increased significantly, and urinary excretion of TP metabolites, 1,3-dimethyluric acid (DMU) and 1-methyluric acid (1MU) decreased significantly [10].

Anatomical context of Ba 2751

• The formation of 1,3-dimethyluric acid was decreased to 30% of the control value in microsomes of cirrhotic rat liver [11].

Associations of Ba 2751 with other chemical compounds

• 5. Ethanol inhibited the formation of 1,3-dimethyluric acid with K(i) value of 300 microM, a value which is consistent with inhibition of CYP2E1 [12].
• Western blot analysis revealed that telithromycin significantly decreased the protein levels of CYP1A2 and CYP3A2 in the liver, which could explain the observed decreases in the systemic clearance of theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric acid [13].

Gene context of Ba 2751

• RATIONALE: The enzyme theophylline oxidase is used in this assay kit to convert theophylline to 1,3 dimethyluric acid in the presence of cytochrome C. Cytochrome C is reduced to ferrocyte C, which is then measured by ultraviolet spectrophotometry at one minute and again at five minutes [14].

Analytical, diagnostic and therapeutic context of Ba 2751

• The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC [11].
• When used in a homogeneous enzyme immunoassay for theophylline these antibodies show insignificant cross-reactivity (less than 1%) to 1-methyl- and 1,3-dimethyluric acid, 3-methylxanthine, caffeine, and theobromine [15].

References