We measured aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes. A striking seasonal variation in AHH activity was observed with induced AHH activity levels from January through May measuring approximately 20% of the values during the remainder of the year. AHH inducibility was determined by comparing lymphocytes from the same person cultured with and without the inducer 3-methylcholanthrene. If measurements are limited to the summer and fall seasons when AHH activity is high, AHH inducibility is reproducible for most persons with repeat determinations on the same person averaging 11% from the mean. The values of AHH inducibility in 53 persons ranged from 0.9 to 5.0, but the distribution of values did not fall into three distinct, nonoverlapping classes as reported by others. We were not able to determine the distribution of AHH inducibility in lung cancer patients since lymphocytes from less than half of the patients tested could be successfully cultured.
Environmental exposure to carcinogens may contribute to increasing breast cancer rates and geographic variation in breast cancer incidence in the United States. One class of chemicals that has received much attention are the polyaromatic hydrocarbons that are ubiquitous in the environment and occur in cigarette smoke. The cytochrome P450 1A1 (CYP1A1) gene codes for an enzyme that contributes to aryl hydrocarbon hydroxylase activity, which is involved in the metabolism of polyaromatic hydrocarbons. Genotypic variants of CYP1A1 have been associated with increased aryl hydrocarbon hydroxylase activity, and some epidemiological studies suggest that women with the variant genotype(s) are at increased risk for breast cancer.. We prospectively evaluated the associations between the CYP1A1 polymorphisms and breast cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case-control study nested within the Nurses Health Study. We analyzed the T→C transition ...
Closer evaluation of the superimposed SIRT2 structures revealed that the amide group of 6 might occupy the same space as the methyl group of the Nε-acetyl-lysine substrate (Fig. 3). This result prompted us to take a new perspective toward targeting the substrate-binding site through the functionalization of the benzamide moiety in 6 to mimic the acetyl-lysine interactions, which afforded compounds 17-19, 26-28, 36, 41 and 42 (Fig. 4). All compounds prepared in this study (Schemes S1-4†) were screened in vitro against SIRT1-3 and SIRT5 (concentration: 10 μM; Table 1), while 6, UKU10363 (Fig. 4) and 5 were used as reference compounds. In a first attempt to mimic the lysine acetyl amide, we explored small fragments using a glycinamide linker (17-19). The screening of SIRT1-3 and 5 (Table 1) revealed that both isotype selectivity and good SIRT2 inhibitory activity were retained upon amide functionalization of 6, although the inhibitory potency was not improved. In order to rationalize the ...
Some, but by no means most, of the individual variability in the rate at which nicotine is metabolized can be explained by CYP2A6 SNPs. Generally, smokers whose bodies rapidly metabolize nicotine will smoke more cigarettes, take in more cigarette smoke, and be more resistant to kicking the habit than slower metabolizers. The most common CYP2A6 allele, CYP2A6*1, is considered to give rise to a fast metabolizing phenotype. Four relatively common CYP2A6 alleles are associated with slower metabolizers; they are CYP2A6*2, CYP2A6*4, CYP2A6*9, and CYP2A6*12. [PMID 17112802] CYP2A6*5 is a rare non-functioning variant. [PMID 15993850] The CYP2A6*20 variant results in a truncated protein and no enzyme activity. To be more precise, the estimated percentage of CYP2A6 activity by genotype is as follows: ...
To test whether the distribution of AHH inducibility is shifted toward the high end of the range in patients who had lung and laryngeal cancer, we measured this trait in 59 patients (32 lung and 27 laryngeal) who had resectable tumors and had been disease-free for a period of time. The advantage of selecting patients who were free of clinical disease was that measurement of their AHH inducibility should not have been affected by the disease state. Patient and control populations showed no difference in basal and induced AHH activity of AHH inducibility. The mean AHH inducibility in patients who had lung cancer was 3.20 +/- 0.20; in patients who had laryngeal cancer 2.96 +/- 0.18, and for all controls 3.29 +/- 0.04 (no significant difference at p = 0 05). Further analysis of the distribution of AHH inducibility in the patient group compared to controls showed no suggestion of a shift toward the higher end of the range in patients who had lung and laryngeal cancer.
TAK-677 has no effect on 24-h RQ or fat oxidation but does slightly increase 24-h EE at the highest dose (0.5 mg BID). The acute studies showed large interindividual variability in plasma concentrations of TAK-677 indicating some possible problems with bioavailability and therefore efficacy.
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TY - JOUR. T1 - Metabolic activation of aromatic hydrocarbons in purified rat liver nuclei. T2 - induction of enzyme activities and binding to DNA with and without monooxygenase catalyzed formation of active oxygen. AU - Rogan, Eleanor G. AU - Mailander, P.. AU - Cavalieri, Ercole. PY - 1976/1/1. Y1 - 1976/1/1. N2 - Purified rat liver nuclei covalently bound low levels of seven aromatic [14C]hydrocarbons to nuclear DNA. Iduction with 3 methylcholanthrene increased the binding of six carcinogenic hydrocarbons, but did not raise the level of binding of noncarcinogenic anthracene. Removal of the nuclear envelope by Triton N 101 eliminated binding and aryl hydrocarbon hydroxylase activities and cytochrome P 450 from the nuclei. Binding of two strong carcinogens, benzo[α]pyrene and 7,12 dimethylbenz[α]anthracene, to nuclear DNA was compared to the levels of aryl hydrocarbon hydroxylase and cytochrome P 450 in nuclei from uninduced and benz[α]anthracene, 3 methylcholanthrene, and phenobarbital ...
MalaCards based summary : Cyp1b1-Related Primary Congenital Glaucoma is related to primary congenital glaucoma. An important gene associated with Cyp1b1-Related Primary Congenital Glaucoma is CYP1B1 (Cytochrome P450 Family 1 Subfamily B Member 1 ...
The response of intestinal monooxygenases to dietary polycyclic aromatic hydrocarbon (PAH) exposure was evaluated in spot (Leiostomus xanthurus), a marine teleost fish. Ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) activities were highest in the pyloric caeca and in the proximal half of the intestine. Intestinal microsomes from fish given control diets had very low levels of EROD and AHH activities relative to those in liver. After exposure to a diet containing 10 mg of 3-methylcholanthrene/kg of food, the levels of intestinal EROD and AHH activities increased 36-fold and 17-fold, respectively, such that intestinal monooxygenase activity exceeded that of the liver, which was not induced by this treatment. A significant increase in intestinal monooxygenase activity occurred in fish receiving dietary benzo[a]pyrene (BP) at concentrations as low as 10 micrograms of BP/kg food. A 5-fold increase in intestinal AHH and EROD activities was observed within 3 hr after ...
The c1 (B6NLxv1c2) line was derived from Hepa-1c1c7 (ATCC CRL-2026). Hepa-1c1c7 has high CYP1A1-dependent aryl hydrocarbon hydroxylase (AHH) activity. N-methyl-N-nitro-N-nitrosoguanidine (MNNS) mutated colonies were selected for benzo[a]pyrene resistance. The c1 (B6NLxv1c2) cell line lacks cytochrome P4501A1 dependent aryl hydrocarbon hydroylase (AHH) activity due to a single point mutation in CYP1A1 leading to premature termination of the translated protein (Asn-414; 56 kDa to 45 kDa). The line may be used to study xenobiotic (and carcinogenic) metabolism in the absence of cytochrome P4501A1 activity, which is known to metabolize cytotoxic and carcinogenic intermediates. It is also a tool to study the putative natural ligand for the induction of this enzyme.
Experimental results, as well as theoretical approaches, indicate one route for substrate access, pw2a, that is common to P450s. Pw2a may also serve as a product egress route in some P450s (Gerber, 1994; Lüdemann et al, 2000a, 2000b; Prasad et al, 2000; Mueller et al, 2003), such as soluble bacterial proteins. However, for membrane‐bound P450s, the pws for product egress and substrate access are likely to differ. A hydrophobic substrate is likely to enter the active site of the enzyme from the membrane, along pw2a; a hydroxylated water‐soluble product is likely to be released into the cytoplasm and requires a different pathway (Fig 2).. The number of crystal structures of mammalian P450s available is limited and the enzymatic mechanism of membrane‐bound P450s is poorly understood. Recently, the first crystal structure of a mammalian membrane‐associated P450 (CYP2C5) in complex with a substrate, 4‐methyl‐N‐methyl‐N‐(2‐phenyl‐2H‐pyrazol‐3‐yl) benzenesulphonamide (DMZ), ...
Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development. Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity ...
Stable expression of human cytochrome P4502E1 in HepG2 cells: characterization of catalytic activities and production of reactive oxygen intermediates.: Experim
Trichloroepoxypropane: A potent epoxide hydrase and aryl hydrocarbon hydroxylase inhibitor. It enhances the tumor-initiating ability of certain carcinogens.
Authors: Goldstone, J.V., A.G. McArthur, A. Kubota, J. Zanette, T. Parente, M. Jönsson, D.R. Nelson, & J.J. Stegeman. BMC Genomics 2010, 11: 643.. Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development. Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human ...
CYP46A1 antibody [N1C2] (cytochrome P450, family 46, subfamily A, polypeptide 1) for WB. Anti-CYP46A1 pAb (GTX105183) is tested in Mouse samples. 100% Ab-Assurance.
CYP51A1 antibody (cytochrome P450, family 51, subfamily A, polypeptide 1) for WB. Anti-CYP51A1 pAb (GTX108762) is tested in Human samples. 100% Ab-Assurance.
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This thing that the doc said hed done thousands of times before and would only take a minute was an ordeal. Apparently I am a "fast metabolizer" of anesthetics. This means that it takes more than the usual patient to where I cant feel anything. Of course this also means more shots! Whats the way to determine that one is a fast metabolizer? Have someone start cutting something off your head so that you can say, "OW!!" I am not exaggerating...FOUR shots later, I finally dont feel anything and he was able to run me over the deli slicer. Ok, so he didnt do that, but it was pretty bad! When I was able to sit up, I turned a little pale and they wouldnt let me up right away, Sylvia looked at the spot on my head and grimaced. She tried to hide it but I could tell. She was a little horrified. I finally got out of her that there was a good sized lump on my head where he took it off. I said, "Of course theres a lump! Thats what happens when you pump a quart and a half of Novocaine into someones ...
ウサギ・ポリクローナル抗体 ab95047 交差種: Ms,Hu 適用: WB,IHC-P,Flow Cyt…CYP27B1抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
The research and development of new drugs is a complex time-and cost-consuming process. Today the mechanism-based approach dominates.
Rabbit anti-human cytochrome P450 enzyme CYP3A4 (polyclonal antibody). Heme-thiolate monooxygenase, involved in metabolism of several steroids, fatty acids, and xenobiotics. CYP3A4 & 5 are the two most predominant proteins within the CYP3A subfamily in human adults, which are collectively involved with the biotransformation of 50% of oxidatively metabolised drugs1. CODE NUMBER: R2X.. QUANTITY: 0.1 mL.. SPECIFICITY: Reacts with human cytochrome P450 enzyme CYP3A4 in hepatic microsomal. fraction from adult donors. Also binds to the fetal form: CYP3A7. No cross-reactivity with CYP3A5.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot, immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Human.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in undiluted aliquots for up to 12 months. Avoid repeated freeze/thaw cycles.. For research ...
Using AGM as a model, we found that long-term, in vivo nicotine treatment significantly decreases in vitro nicotine metabolism by approximately 40% and the expression of a CYP2A6-like protein in AGM liver by approximately 60%. Because nicotine metabolism is dose-independent at the levels of nicotine self-administered by smokers (Benowitz and Jacob, 1993), changes in CYP2A6 protein would be expected to alter nicotine metabolism. Experiments using anti-CYP2A6 inhibitory antibodies strongly suggest that the decrease in nicotine metabolism after long-term nicotine administration is mediated by the decrease observed in the CYP2A6agm-mediated portion of the total NCO (40%), similar to the reduction observed in CYP2A6agm protein (60%). This is quantitatively similar to the decreases in nicotine clearance observed during smoking compared with nonsmoking (27-34%; Lee et al., 1987;Benowitz and Jacob, 1993). Our observation that CYP2A6agm protein and nicotine metabolism is reduced in AGM that underwent ...
Graham, Kirsty, Sparagano, Olivier, Pérez de Léon, Adalberto, Bell-Sakyi, Lesley, Guerrero, F. and Finn, Robert (2012) Identification of Novel Cytochrome P450s in the Acari. In: 19th International Symposium on Microsomes and Drug Oxidations and 12th European ISSX Meeting, 17-21 June, 2012, Noordwijk aan Zee, the Netherlands. Full text not available from this repository. (Request a copy ...
Recombinant Cytochrome P450, Family 1, Subfamily A, Polypeptide 2 (CYP1A2) Protein. Species: Human. Source: Escherichia coli (E. coli). Order product ABIN6303723.
Clopidogrel has anti-platelet activity by irreversible inhibition of the P2Y12 platelet receptor. Clopidogrel must be converted into an active metabolite in order to show anti-platelet activity. Hepatic CYP2C19 enzyme is one of the key hepatic enzymes which convert clopidogrel into active metabolite and its genetic polymorphism is related to clopidogrel resistance. CYP2C19 poor or intermediate metabolizer groups show reduced anti-platelet activity of clopidogrel compared to extensive metabolizer group ...
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Each CypExpress product is comprised of a specific, unmodified recombinant human CYP, P450 oxidoreductase cofactors, and antioxidants encapsulated in a semipermeable shell - allowing rapid diffusion of substrates and products.
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Health, ... Selecting Patients Based on Genotype May Increase Efficacy of Tamox...Breast cancer patients who carry the wild-type gene required for tamox...Cytochrome P450 2D6 (CYP2D6) converts tamoxifen into its metabolically...To estimate whether women with wild-type CYP2D6 might derive m...,Other,highlights,in,the,April,29,JNCI,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is
Recombinant protein of human cytochrome P450, family 51, subfamily A, polypeptide 1 (CYP51A1), 20 ug available for purchase from OriGene - Your Gene Company.
Melet, A., Marques-Soares, C., Schoch, G. A., Macherey, A. C., Jaouen, M., Dansette, P. M., Sari, M. A., Johnson, E. F., Mansuy, D. Analysis of human cytochrome P4502C8 substrate specificity using a substrate pharmacophore and site-directed mutants Biochemistry 2004 43:15379-15392 DOI:10.1021/bi0489309 PMID:15581350 ...
The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A , G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02 ± 1.56 vs. 5.96 ± 2.01 mg; p = 0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model ...
TY - JOUR. T1 - Selective deficiency of debrisoquine 4-hydroxylase activity in mouse liver microsomes. AU - Masubuchi, Yasuhiro. AU - Iwasa, Takashi. AU - Hosokawa, Shin. AU - Suzuki, Tokuji. AU - Horie, Toshiharu. AU - Imaoka, Susumu. AU - Funae, Yoshihiko. AU - Narimatsu, Shizuo. PY - 1997/9. Y1 - 1997/9. N2 - Cytochrome P450 enzymes belonging to the CYP2D subfamily have been shown to be one of determinants of the polymorphic drug oxidations in the human and the rat. Debrisoquine 4-hydroxylation is a typical reaction catalyzed by these enzymes. However, various strains of mice were observed to have much lower debrisoquine 4-hydroxylase activity than Wistar rats, whereas other monooxygenase activities in mice toward bunitrolol, propranolol, imipramine and amitriptyline, which are mediated by the CYP2D enzymes in the rat, were comparable to those of the rats. Immunoblot analysis of mouse liver microsomes with an antibody raised against a rat CYP2D enzyme indicated that the mouse liver contained ...
Rabbit anti-human cytochrome P450 enzyme CYP2D6 (polyclonal antibody). O-demethylation of xenobiotics, CYP2D6 is involved in the metabolism and elimination of approximately 25% of clinically used drugs in humans1. Primarily expressed in the liver and areas of the CNS. CYP2D1 and CYP2D4 have a similar function in rats2.. CODE NUMBER: RT01.. QUANTITY: 0.1 mL.. SPECIFICITY: Reacts with human cytochrome P450 enzyme CYP2D6 in hepatic microsomal fraction. No cross-reactivity with other cytochrome P450 enzymes.. IMMUNOGEN: Synthetic peptide.. SUGGESTED APPLICATIONS: Western blot, immunohistochemistry on frozen and formaldehyde treated sections. Optimal working dilutions must be determined by end user.. SPECIES REACTIVITY: Human.. FORMAT: Rabbit antiserum.. PRESENTATION: Liquid. No preservatives.. STORAGE/HANDLING: Maintain at -20°C in undiluted aliquots for up to 12 months. Avoid repeated freeze/thaw cycles.. For research use only; not for use in diagnostic procedures. Not for human or animal ...
The anticoagulant effect of warfarin varies greatly among individuals. Some of this variability is attributed to differences in the activity of CYP2C9, the predominant enzyme involved in the metabolism of S-warfarin.. The present study is designed to define the differences in warfarin metabolism among healthy individuals carrying different CYP2C9 genotypes. In addition, the study will define the correlation between the phenytoin metabolic ratio, a marker of CYP2C9 activity in vivo, and warfarin metabolism. ...
Primary congenital glaucoma is characterized by photophobia, epiphora, and blepharospasm. Read about hereditary, causes, symptoms, treatment, risk factors, and prognosis.
There are no specific protocols for Recombinant Human Constitutive androstane receptor protein (ab81846). Please download our general protocols booklet
In this article, we describe the generation and characterization of a novel CYP3A4 humanized mouse line that carries a replacement of the seven chromosomally closely linked murine Cyp3a genes with a large human genomic region carrying CYP3A4 and CYP3A7. A similar approach to replace large sequences of mouse genomic DNA with a syntenic region of human DNA was recently described for the α globin regulatory domain (Wallace et al., 2007). The use of a modified strategy allowed us to generate knockout control mice, Cyp3a(−/−)/3a13(+/+), carrying a deletion of the major part of the mouse Cyp3a cluster. Furthermore, because we used a different selection marker, our approach can be applied to any eukaryotic cell type and can therefore be used widely for the exchange of genomic regions between species.. The targeted insertion strategy applied in the present work distinguishes our huCYP3A4/3A7 model from other existing CYP3A4 humanized mouse lines. Compared with the random transgenic mouse line ...
This study is the first report in which P450s involved in the two oxidative steps required for the metabolism of clopidogrel to its active metabolite are identified and their contributions determined. CYP1A2, CYP2B6, and CYP2C19 are capable of producing 2-oxo-clopidogrel, whereas the remaining isoforms examined were practically inactive in this first oxidative step of clopidogrel. Savi et al. (1994) suggested that rat CYP1A was involved in the active metabolite formation from clopidogrel. The present study confirmed that CYP1A2 does indeed contribute to the first oxidative step of this metabolic process. Regarding the second metabolic step, formation of clopidogrel active metabolite was catalyzed by CYP2B6, CYP2C9, CYP2C19, and CYP3A4. The reaction mixture for the active metabolite formation contained glutathione, because it was previously shown that formation of a thienopyridines active metabolite required the presence of both P450s and a reducing agent such as glutathione in the incubation ...
BioAssay record AID 769674 submitted by ChEMBL: Drug metabolism in human liver microsomes assessed as CYP3A4-mediated metabolite formation in presence of ketaconozole.
BioAssay record AID 510137 submitted by ChEMBL: Ratio of IC50 for CYP3A4 in human liver microsomes measured immediately to IC50 for CYP3A4 in human liver microsomes measured after incubation.
Sigma-Aldrich offers abstracts and full-text articles by [Ramakrishna Nirogi, Raghava Choudary Palacharla, Abdul Rasheed Mohammed, Arunkumar Manoharan, Ranjith Kumar Ponnamaneni, Gopinadh Bhyrapuneni].
Phenytoin (PHT) oxidative route leads to its main metabolite p-hydroxyphenytoin (p-HPPH), by means of CYP2C9 and CYP2C19. Formation of p-HPPH proceeds via a reactive arene-oxide intermediate. This intermediate can also be converted into PHT dihydrodiol by microsomal epoxide hydrolase (EPHX). The three enzymes are polymorphically expressed and the genetic variants are responsible for changes in the enzyme activity. In order to evaluate the effect that these polymorphisms have on PHT metabolism, PHT and p-HPPH plasma concentrations were measured and the genotype for the three enzymes was assessed in 50 Uruguayan epileptic patients. 30% of the patients were intermediate and 2% were poor metabolizers for CYP2C9, while 20% were intermediate metabolizers for CYP2C19. 44%, 10%, and 46% of subjects had intermediate, increased and decreased activities of EPHX respectively. CYP2C9 was confirmed to be the main responsible enzyme for PHT biotransformation. CYP2C19 seemed to be preponderant in p-HPPH oxidative
UMDNJ-Robert Wood Johnson Medical School researchers have found that carbamazepine and oxycarbamazepine increase nicotine metabolism in smokers.
Abstract OBJECTIVE: In order to evaluate the inhibitory effects of isoniazid on cytochrome P450 (CYP) mediated drug metabolism, the in vitro inhibitory potency and specificity as w..