FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1543737679> ?p ?o ?g. }

• W1543737679 endingPage "838" @default.
• W1543737679 startingPage "836" @default.
• W1543737679 abstract "Cigarette smoking accelerates the metabolism of certain drugs, particularly those primarily metabolized by cytochrome P450 1A2 (CYP1A2) and, to a lesser extent, CYP2E1 and some UDP-glucuronosyltransferases [1, 2]. The induction of CYP1A2 is mediated by binding of polycyclic aromatic hydrocarbons of the tobacco smoke to the aryl hydrocarbon receptor (AHR) with consequent transcriptional activation of the CYP1A2 gene. Furthermore, CYP1A1 and CYP1B1 enzymes are induced by tobacco smoking via AHR in various human tissues such as lung and placenta [3]. As CYP1A1 and CYP1B1 are mostly expressed in extrahepatic tissues, their induction by smoking is not known to affect the pharmacokinetics of any medication. There is evidence of the role of nicotine in the induction of CYP1A1 and CYP1A2 enzymes in vitro in rat lung [4], and in vivo in rat lung, kidney and liver [5–7], liver and placenta of pregnant rats [8] and in brains of mice and rats [9, 10], probably through mechanisms not involving AHR. Some evidence exists for the induction of CYP1A1 by nicotine in human pulmonary explant culture [11]. We recently published a study on the effects of 10 day dosing of nicotine on human CYP2A6 and CYP2E1 activities [12]. An additional aim of that study was to determine the effects of high dose nicotine on the pharmacokinetics of oral caffeine and to test the hypothesis that nicotine induces CYP1A2-mediated metabolism of caffeine to paraxanthine, a well-established probe reaction of CYP1A2 activity [13]. No previous study has studied the effects of nicotine on CYP1A2 activity in humans in vivo. The details of the experimental protocol and the subject characteristics are described in a prior report [12]. Briefly, 12 healthy smokers were given two 21 mg transdermal patches delivering a total of 42 mg nicotine day−1 or placebo patches, each for 10 days in a randomized and crossover design. Subjects were not allowed to smoke or to use any tobacco products during hospitalization. At noon on the eighth hospital day, 200 mg of oral caffeine was given. Blood samples were collected for measurement of caffeine and metabolites at 0, 30 and 60 min, and then 2, 3, 4, 6, 8, 12, 20, 32, 44 and 52 h after ingestion of caffeine. In addition, deuterium-labelled nicotine-D2 and cotinine-D4 phenotyping for CYP2A6, bupropion phenotyping for CYP2B6 and chlorzoxazone phenotyping for CYP2E1 were performed on the seventh and eighth hospital days as previously described [12]. Concentrations of caffeine, paraxanthine, theobromine and theophylline in plasma were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Stable isotope-labelled analogues of paraxanthine and caffeine were used as internal standards. Following protein precipitation, samples (0.2 ml) were treated with phosphate buffer and extracted with a mixture of methylene chloride, ethyl acetate and isopropyl alcohol. The extracts were evaporated, reconstituted in the LC mobile phase, and injected into the LC-MS/MS system. The mass spectrometer was operated using atmospheric pressure chemical ionization, and selected reaction monitoring was used for quantitation. Calibration curves were constructed using the peak area ratio of analyte : internal standard and linear regression. Limits of quantitation for all analytes were 10 ng ml−1. Precision (within-run, % coefficient of variation) ranged from 1.7 to 10.3%, and accuracy (% of expected value) ranged from 88 to 118% for concentrations from 10 ng ml−1 to 5000 ng ml−1. Oral clearance of caffeine was computed as follows: CL = Dose/AUC. The oral CL of caffeine and the paraxanthine : caffeine AUC(0,52 h) ratio were used as measures of CYP1A2 activity. The pharmacokinetic parameters were compared across treatments by paired Student's t-test. The effects of nicotine on the disposition kinetics of caffeine are presented in Table 1. There was no significant influence of nicotine administration on the pharmacokinetic parameters of caffeine or the formation pharmacokinetics of paraxanthine, theophylline and theobromine. Since caffeine metabolism to paraxanthine is a specific probe reaction for CYP1A2 [13], it can be concluded that CYP1A2 activity is not affected by 8 days of nicotine dosing. Although previous studies in experimental animals have provided evidence for the role of nicotine in the induction of CYP1A1 and CYP1A2 enzymes [4–10], our study disproves the hypothesis that nicotine induces CYP1A2 activity in humans in vivo. The discrepancy between human and animal data may be explained by tissue and species specific expression patterns. The human caffeine phenotyping probes the hepatic CYP1A2 activity, whereas the animal studies are mainly on extrahepatic CYP1A1 induction or based on methods not capable of differentiating between CYP1A1 and CYP1A2 enzymes. In addition to nicotine and caffeine, bupropion and chlorzoxazone were administered during the study to phenotype CYP2B6 and CYP2E1 activities, respectively. We are not aware of any clinical studies demonstrating that bupropion inhibits CYP1A2 activity. In human liver microsomes in vitro, bupropion incubated with melatonin or phenacetin (probes for CYP1A2) shows no inhibitory effects on CYP1A2-mediated pathways [14–16]. Chlorzoxazone and caffeine have been dosed together in several metabolic cocktail approaches to phenotype CYP enzymes without any detected metabolic interactions [17–19]. Thus, there is no known interaction between the study medications affecting the phenotyping of CYP1A2. In conclusion, this study shows that human CYP1A2 activity is not affected by nicotine and provides evidence that high dose nicotine treatment has a low potential for interaction with concurrently administered CYP1A2 substrates. Nicotine has no role in the induction of CYP1A2 that is known to occur in smokers. Dr Benowitz has been a paid consultant to several pharmaceutical companies that are developing or market smoking cessation medications. We thank Brenda Herrera and Sandra Tinetti and the staff of the General Clinical Research Center at San Francisco General Hospital for assistance in conducting the clinical study, as well as Sylvia Wu and Lita Ramos for performing analytic chemistry procedures and Dr Faith Allen for help in data management. The study was supported by US Public Health Service grants DA02277 and DA12393 from the National Institute on Drug Abuse, National Institutes of Health, and grants from the Academy of Finland, the Paavo Nurmi Foundation, the Finnish Cultural Foundation, and the Finnish Medical Foundation to J.H. The study was carried out in part at the Clinical Research Center at San Francisco General Hospital Medical Center with the support of NIH/NCRR UCSF-CTSI grant UL1 RR024131." @default.
• W1543737679 created "2016-06-24" @default.
• W1543737679 creator A5014763287 @default.
• W1543737679 creator A5050586835 @default.
• W1543737679 creator A5073258440 @default.
• W1543737679 creator A5083971769 @default.
• W1543737679 creator A5084607207 @default.
• W1543737679 date "2011-10-11" @default.
• W1543737679 modified "2023-10-17" @default.
• W1543737679 title "Effect of nicotine on cytochrome P450 1A2 activity" @default.
• W1543737679 cites W1872908422 @default.
• W1543737679 cites W1972960173 @default.
• W1543737679 cites W1974472457 @default.
• W1543737679 cites W1984409435 @default.
• W1543737679 cites W1993282118 @default.
• W1543737679 cites W2010985370 @default.
• W1543737679 cites W2013789561 @default.
• W1543737679 cites W2025756285 @default.
• W1543737679 cites W2034400329 @default.
• W1543737679 cites W2046877204 @default.
• W1543737679 cites W2063930684 @default.
• W1543737679 cites W2075870841 @default.
• W1543737679 cites W2077067141 @default.
• W1543737679 cites W2093703284 @default.
• W1543737679 cites W2102053457 @default.
• W1543737679 cites W2137538945 @default.
• W1543737679 cites W2157604431 @default.
• W1543737679 cites W2164206878 @default.
• W1543737679 doi "https://doi.org/10.1111/j.1365-2125.2011.04023.x" @default.
• W1543737679 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3243019" @default.
• W1543737679 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21599724" @default.
• W1543737679 hasPublicationYear "2011" @default.
• W1543737679 type Work @default.
• W1543737679 sameAs 1543737679 @default.
• W1543737679 citedByCount "48" @default.
• W1543737679 countsByYear W15437376792015 @default.
• W1543737679 countsByYear W15437376792016 @default.
• W1543737679 countsByYear W15437376792017 @default.
• W1543737679 countsByYear W15437376792018 @default.
• W1543737679 countsByYear W15437376792019 @default.
• W1543737679 countsByYear W15437376792020 @default.
• W1543737679 countsByYear W15437376792021 @default.
• W1543737679 countsByYear W15437376792022 @default.
• W1543737679 countsByYear W15437376792023 @default.
• W1543737679 crossrefType "journal-article" @default.
• W1543737679 hasAuthorship W1543737679A5014763287 @default.
• W1543737679 hasAuthorship W1543737679A5050586835 @default.
• W1543737679 hasAuthorship W1543737679A5073258440 @default.
• W1543737679 hasAuthorship W1543737679A5083971769 @default.
• W1543737679 hasAuthorship W1543737679A5084607207 @default.
• W1543737679 hasBestOaLocation W15437376792 @default.
• W1543737679 hasConcept C126322002 @default.
• W1543737679 hasConcept C185592680 @default.
• W1543737679 hasConcept C2779547902 @default.
• W1543737679 hasConcept C526171541 @default.
• W1543737679 hasConcept C62231903 @default.
• W1543737679 hasConcept C71924100 @default.
• W1543737679 hasConcept C86745063 @default.
• W1543737679 hasConcept C98274493 @default.
• W1543737679 hasConceptScore W1543737679C126322002 @default.
• W1543737679 hasConceptScore W1543737679C185592680 @default.
• W1543737679 hasConceptScore W1543737679C2779547902 @default.
• W1543737679 hasConceptScore W1543737679C526171541 @default.
• W1543737679 hasConceptScore W1543737679C62231903 @default.
• W1543737679 hasConceptScore W1543737679C71924100 @default.
• W1543737679 hasConceptScore W1543737679C86745063 @default.
• W1543737679 hasConceptScore W1543737679C98274493 @default.
• W1543737679 hasIssue "5" @default.
• W1543737679 hasLocation W15437376791 @default.
• W1543737679 hasLocation W15437376792 @default.
• W1543737679 hasLocation W15437376793 @default.
• W1543737679 hasLocation W15437376794 @default.
• W1543737679 hasOpenAccess W1543737679 @default.
• W1543737679 hasPrimaryLocation W15437376791 @default.
• W1543737679 hasRelatedWork W1974734452 @default.
• W1543737679 hasRelatedWork W1979766887 @default.
• W1543737679 hasRelatedWork W2021893169 @default.
• W1543737679 hasRelatedWork W2056942052 @default.
• W1543737679 hasRelatedWork W2061788598 @default.
• W1543737679 hasRelatedWork W2105068995 @default.
• W1543737679 hasRelatedWork W2117987021 @default.
• W1543737679 hasRelatedWork W2133617154 @default.
• W1543737679 hasRelatedWork W3192835915 @default.
• W1543737679 hasRelatedWork W4282918893 @default.
• W1543737679 hasVolume "72" @default.
• W1543737679 isParatext "false" @default.
• W1543737679 isRetracted "false" @default.
• W1543737679 magId "1543737679" @default.
• W1543737679 workType "article" @default.