Spot urine samples obtained 6 hours following 200-mg caffeine administration were used to determine caffeine metabolite ratios (CMRs); blood samples were used to determine CYP1A2*1F (rs762551) and CYP1A2*1C (rs2069514) polymorphisms and the hormonal profile (estradiol, progesterone, and luteinizing and follicle-stimulating hormones) at EFP, LFP, and LP.
Some common genes that are included in nutrition-based multigene test panels include CYP1A2 (rate of caffeine break down), MTHFR (folate usage), NOS3 (risk of elevated triglyceride levels related to omega-3 fat intake), and ACE (blood pressure response in related to sodium intake).
The effects of caffeine on basketball performance were established according to players' CYP1A2 genotype (rs762551): AA homozygotes (n = 10) and C-allele carriers (n = 9).
A sensitive, specific, and fast ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for determination of caffeine (probe of CYP1A2), tolbutamide (probe of CYP2C9), dextromethorphan (probe of CYP2D6), and alprazolam (probe of CYP3A4/5) in human serum.
The seven-drug cocktail was composed of caffeine, bupropion, tolbutamide, omeprazole, dextromethorphan, midazolam (all administered concomitantly) and chlorzoxazone (administered separately) to phenotype for CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5 and 2E1, respectively.
The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo-controlled, crossover study.
Enzyme phenotyping was assessed in saliva and urine using caffeine and paracetamol metabolite ratios as follows: CYP1A2: 17X/137X (saliva) and (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X), NAT2: AFMU/(AFMU+1U+1X) and UGT1A1/1A6: glucuronidated/total paracetamol (urine).
A previous clinical study of obeticholic acid (OCA) with caffeine suggested that OCA may be a useful positive control to establish a method to evaluate CYP1A2 downregulation and to investigate the mechanism of its downregulation.
We used BLUES to investigate binding modes of caffeine in the active site of its metabolizing enzyme Cytochrome P450 1A2 with the aim of elucidating metabolite-formation profiles at different concentrations.
Here, we briefly review the drivers of this inter-individual variation in caffeine response, focusing on the impact of common polymorphisms within two genes, CYP1A2 and ADORA2A.
The effect of tivantinib doses on the pharmacokinetics of the probe drugs for CYP1A2 (caffeine), CYP2C9 (S-warfarin), CYP2C19 (omeprazole), and CYP3A4 (midazolam), and for P-glycoprotein (digoxin) was investigated in 28 patients with advanced cancer using a cocktail probe approach.
This study aimed to examine whether functional single nucleotide polymorphisms (SNPs) in 1976T > C (ADORA2A; rs5751876) and -163C > A (CYP1A2; rs762551) influence the effect of caffeine on the postprandial glucose (GLU) response to a carbohydrate meal.
However, the use of a stratified value of CYP1A2 content derived from a Han Chinese cohort with a small sample size instead of the pooled value of all Chinese cohorts involved regardless of Chinese sub-ethnicity resulted in inadequate prediction of CYP1A2-mediated pharmacokinetics in terms of caffeine and theophylline in either young or elderly Chinese subjects.
Specifically, the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with carriers of the C allele considered to be of a 'slow' metaboliser phenotype.
CYP1A2 activity was assessed 2 hours after the ingestion of a drink containing caffeine through measurement of the metabolic ratio of paraxanthine (17X) over caffeine (137X) by LC-MS/MS or LC-UV.
Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin).
Caffeine has also been shown to undergo 3-demethylation by CYP1A2, and it is further acetylated to 5-acetylamino-6-formylamino-3-methyluracil (AFMU) by the polymorphic NAT2.
Caffeine has been used as a metabolic probe to determine the relative levels of CYP1A2 activity in different individuals, since this compound is specifically 3-demethylated by CYP1A2.