Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites

Butler, Mary Ann; Lang, Nicholas P.; Young, Jette F.; Caporaso, Neil E.; Vineis, P; Hayes, Richard B.; Teitel, Candee H.; Massengill, Joyce; Lawsen, M F; Kadlubar, Fred F.

doi:10.1097/00008571-199206000-00003

Cited by 394 publications

(224 citation statements)

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“…The caffeine test was performed using a modification of the method reported by Nakajima et al 10 and Butler et al 11 Patients refrained from consuming methylxanthincontaining foods, beverages and drugs from the previous day until finishing the test. On the day of the test, early in the morning before breakfast, each patient was given canned coffee (190 g; KIRIN Beverage Co. Ltd.) containing about 150 mg caffeine, to drink.…”

Section: Methodsmentioning

confidence: 99%

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Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer

Ozono

Yamaguchi

Mochizuki

et al. 2002

Prostate Cancer Prostatic Dis

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The caffeine test measures the activity of cytochrome P450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1) five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2) four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3) two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4 -5 h later. The metabolite ratio, (17U þ 17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98 AE 1.56) and the mildly injured group (5.55 AE 1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.

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Section: Methodsmentioning

confidence: 99%

“…10 -12 The urinary metabolite ratio, (17X þ 17U)/137X, was calculated to serve as an indicator of CYP1A2 activity. 10,11 The statistical significance of any differences was tested using Tukey's test.…”

Section: Methodsmentioning

confidence: 99%

Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer

Ozono

Yamaguchi

Mochizuki

et al. 2002

Prostate Cancer Prostatic Dis

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“…Additionally, we assessed caffeine half life from a caffeine challenge test (adapted from Butler et al 28 ) performed within two weeks of recruitment. We provided participants with appropriate materials and instructions to perform the test at home, and the samples were then returned in a prepaid envelope.…”

Section: Quantification Of Caffeine Intakementioning

confidence: 99%

Maternal Caffeine Intake During Pregnancy and Risk of Fetal Growth Restriction: A Large Prospective Observational Study

Study¹

2009

Obstetrical &Amp; Gynecological Survey

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“…C'est une substance ubiquitaire et relativement non toxique même à fortes doses, métabolisée par la voie de la N-acétylation et recommandée comme marqueur pour la détermination du phé-notype d'acétylation par plusieurs auteurs [26][27][28][29][30][31]. Le métabo-lisme de la caféine a été étudié in vivo et in vitro chez l'Homme et plus d'une dizaine de métabolites urinaires ont été déter-minés par CLHP [31][32][33].…”

Section: Introductionunclassified

“…Le métabo-lisme de la caféine a été étudié in vivo et in vitro chez l'Homme et plus d'une dizaine de métabolites urinaires ont été déter-minés par CLHP [31][32][33]. Le 5-acetamino-6-formylamino-3-méthyluracine ou AFMU et le 1-méthylxanthine ou 1X ont été identifiés comme des métabolites majeurs de la caféine et leur rapport de concentration molaire a permis de phénotyper la NAT2 [12,28,31,34].…”

Section: Introductionunclassified

Détermination du polymorphisme d’acétylation de la N-acétyltransférase 2 dans la population sénégalaise par utilisation du test à la caféine

Touré¹,

Cabral²,

Diop³

et al. 2012

Ann Toxicol Anal

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Résumé -Introduction : L'isoniazide (INH) est métabolisée par une N-acétyltransfèrase (NAT), la NAT2. Il existe de nombreux polymorphismes de la NAT2 qui peuvent être associés à des toxicités ou à des échecs thérapeutiques au cours d'un traitement par INH. Objectif : L'objectif de ce travail est de déterminer l'indice d'acétylation de la NAT2 dans la population sénégalaise afin de les répartir en acétyleurs lents et rapides. Méthodes : L'étude du profil d'acétylation a été effectuée sur des urines de 247 sujets en utilisant la caféine comme marqueur. La proportion molaire du 5-acétamino-6-formylamine-3-méthyluracile (AFMU) sur le 1-méthylxanthine (1X) a été déterminée. La répartition de la population étudiée en phénotype lent ou rapide a été réalisée en se basant sur l'antimode = 0,55. Les sujets possédant un rapport ([AFMU]/[1X]) inférieur à 0,55 sont considérés comme des acétyleurs lents et ceux dont le rapport est >0,55 sont des acétyleurs rapides. Résultats : Les résultats obtenus ont montré une ségrégation en deux modes apparents de capacité d'acétylation dans la population sénégalaise testée avec 63,8 % et 36,2 % d'acétyleurs lents et rapides respectivement. Conclusion : La réponse au traitement de maladies comme la tuberculose dépend du polymorphisme d'acétylation de la NAT2, il est donc important de connaître le phénotype de la NAT2 chez les sujets atteints de tuberculose pour éviter des effets indésirables tels que l'hépatotoxicité ou la neurotoxicité. Mots clés : N-acétyltransférase, polymorphisme, indice d'acétylation, test caféineAbstract -Introduction: Isoniazid (INH) is metabolized by an N-acetyltransferase (NAT), the NAT2. There are many of NAT2 polymorphisms that may be associated to toxicity or therapeutic failure of INH. Objective: The objective of this study is to determine the index of acetylation of NAT2 in the Senegalese population. Methods: The study of the profile of acetylation was performed on urine from 247 subjects using caffeine as a marker. The molar ratio of 5-acetamino-6-formyl amine-3-methyluracil (AFMU) on the 1-methylxanthine (IX) was determined. The distribution of the population studied in slow or fast phenotype was performed based on the antimode = 0.55. Subjects who have ratio ([AFMU]/[IX]) less than 0.55 are considered slow acetylators and those, whose ratio is >0.55, are rapid acetylators. Results:The results showed segregation of two apparent modes of acetylation capacity in the Senegalese population tested with 63.8% and 36.2% of slow and fast acetylators respectively. Conclusion: Response to treatment of diseases such as tuberculosis depends on the polymorphism of NAT2 acetylation, it is significant to know the phenotype of NAT2 in patients with tuberculosis to avoid such side effects as hepatotoxicity or neurotoxicity.

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Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites

Cited by 394 publications

References 0 publications

Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer

Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer

Maternal Caffeine Intake During Pregnancy and Risk of Fetal Growth Restriction: A Large Prospective Observational Study

Détermination du polymorphisme d’acétylation de la N-acétyltransférase 2 dans la population sénégalaise par utilisation du test à la caféine

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