Abstract
May 15, 2009 · Substrate preference was tested by replacing xanthine with 0
2
0 mM) for the CYP1A subfamily and the kinetics of metabolic formation mediated by CYP1A2 indicated substrate-inhibition (Ki range 9-16 mM)
The aim of this review is to know the impact of CYP1A2 and CYP2E1 genes polymorphism on theophylline response
This study provides whole‐body physiologically‐based pharmacokinetic models of the strong index cytochrome P450 (CYP)1A2 inhibitor and moderate CYP 3A4 inhibitor fluvoxamine and of the sensitive CYP 1A2 substrate theophylline
Increased clearance is seen in children (1-16 yr) and in cigarette and Theophylline metabolism was studied using seven human cytochrome P- 450 isoforms (CYPs), namely CYP1A1, 1A2, 2A6, 2B6, 2D6, 2E1 and 3A4, and microsomal epoxide hydroxylase (EH), expressed in human B- lymphoblastoid cell lines
The cytochrome P450 (CYP) enzyme family is the most important enzyme system catalyzing the phase 1 metabolism of pharmaceuticals and other xenobiotics such as herbal remedies and toxic compounds in the environment
For the purpose of the study, we chose midazolam as the CYP3A4 substrate
When NAD + was used, enzyme activity was determined by monitoring the increase in absorbance at 340 nm (Δɛ 340 = 6,220 M −1 ·cm −1) due to NADH production
In vivo Table 4
(Figure 3) If that active site is occupied by The metabolic mechanisms of theophylline catalyzed by cytochrome P450 (CYP450) enzyme have been explored in this work
Guengerich, L
Table of Substrates, Inhibitors and Inducers (including: CYP Enzymes, Clinical index drugs, transporters, and examples of clinical substrates, inhibitors, and inducers)
benzo[a]pyrene and aflatoxin B 1), and several important endogenous compounds (e
While present in most body tissues, CYP enzymes predominantly occupy the liver, intestines, and kidneys, with their highest concentration in the liver
1988; 2:325-340
Awareness of the metabolism of second-generation antipsychotics by the cytochrome P450 (CYP) system can inform the clinician about how to avoid and manage drug-drug interactions involving these enzymes
Therefore, any agents or pathology that alters the cytochrome P450 system or renal function can have a substantial effect on theophylline levels
This article reviews the pharmacokinetics, pharmacodynamics, and clinical implications of macrolide drug interactions, and compares the newer macrolides with the older ones
Theophylline had the highest affinity (apparent Km range 0
13
The study by Faber et al recommends that the dose of CYP1A2 substrates such as Theophylline should automatically be reduced by 10% on cessation of heavy smoking and thereafter be guided by plasma concentration monitoring 5
35 Immunohistochemical studies have suggested that this protein is sparse, if present at all, in fetal liver The vast diversity of cytochrome P450 enzymes in mammals has been proposed to result in large measure from plant-animal warfare, whereby evolution of chemical defenses such as phenolics and chrome (CYP) P450 drug interactions when they are admitted to or discharged from a smoke-free facility
CYP1 family members, including CYP1A1, CYP1A2, and CYP1B1, are induced by aryl hydrocarbon receptors (AhRs)
benzo[a]pyrene and aflatoxin B 1), and several important endogenous compounds (e
They are involved in themetabolism of most medications andare the mechanism by which mostpharmacokinetic drug interactionsoccur
Based on a recent compilation of recommended clinical index substrates of major drug-metabolizing enzymes and cytochrome P450 (CYP) isoforms [], a comprehensive literature search identified caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), theophylline (CYP1A2), and tolbutamide (CYP2C9) as index substrates for which Results
28 ml kg −1 min −1, respectively
Theophylline is cyp 1A2 substrate , ciprofloxacin is 1A2 inhibitor, increasing dose of theophylline causing tachycardia, seizures
g
(3) The enzyme is reduced to the ferrous [Fe 2+] state by the addition of an electron from NADPH cytochrome P450 reductase
An anticonvulsant used to treat various types of seizures and pain resulting from trigeminal neuralgia
A comprehensive list of CYP substrate, inhibitors, inducers needed to be known for the second metabolism exam
Theophylline
S-mephenytoin
or induction of cytochrome P450 Abstract
Although the substrate binding step is depicted as taking place prior to the reduction of the heme iron via the electron provided by NAPDH-P450 reductase, it has been shown that the substrate Abstract
Theophylline is a medicine with narrow therapeutic index
An increasing amount of evidence has suggested that low-dose theophylline has anti-inflammatory and immunomodulatory effects in asthma and COPD, and thus
Theophylline is a typical substrate of cytochrome P450(CYP) 1A2 enzyme in vivo (Nosaka et al
For the purpose of the study, we chose midazolam as the CYP3A4 substrate
We investigated the development changes in the pattern of urinary metabolites of theophylline, a substrate for CYP1A2, to study when CYP1A2, which is absent in the
Drugs that inhibit CYP1A2 will predictably
Inhibition of cytochrome P450 (CYP450) enzymes is the most common mechanism leading to drug–drug interactions
N-demethylation; CYP2A6, coumarin-7-hydroxylation;
Awareness of the metabolism of second-generation antipsychotics by the cytochrome P450 (CYP) system can inform the clinician about how to avoid and manage drug–drug interactions involving these enzymes
5), an appropriate amount of cell extract, and
Many clinical resources for healthcare providers continue to list erythromycin and clarithromycin as inhibitors of cytochrome P4501A2 (CYP1A2) []
2
Theophylline is metabolized in the liver by the cytochrome P450 microsomal enzyme system, and a large number of factors may influence hepatic metabolism
, 2010)
0 mM) for the CYP1A subfamily and the kinetics of metabolic formation mediated by CYP1A2 indicated substrate-inhibition (Ki range 9-16 mM)
Drug Drug Description; Theophylline: Cytochrome P450 2D6: enzyme: Theophylline: Histone deacetylase 2: target: Theophylline: Copine-1: target: Theophylline: Minor histocompatibility antigen
13
The 8-hydroxylation of Theophylline to 1,3-dimethyluric acid (1,3-DMU) via cytochrome P450 1A2 is the major pathway
35 Immunohistochemical studies have suggested that this protein is
The binding of ligands such as polycyclic aromatic hydrocarbons activates the AhRs, which are involved
benzo[a]pyrene and aflatoxin B 1), and several important endogenous compounds (e
CYP1A2 metabolises many clinical drugs, such as phenacetin, caffeine, clozapine, tacrine, propranolol, and mexiletine
CYP1A2 is part of the cytochrome P450 (CYP) family of drug-metabolizing enzymes
Tizanidine (Zanaflex) Triamterene (Dyrenium) Zolmitriptan (Zomig) The cytochrome P450 enzymesare found primarily in the liver,although some (eg, CYP3A4) arealso found in substantial amounts inthe intestine