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.
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.
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 effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo-controlled, crossover study.
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.
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.
Enzyme phenotyping was assessed in saliva and urine using caffeine metabolite ratios as follows: CYP1A2: 17X/137Χ (saliva) and CYP1A2: (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X) and NAT2: AFMU/(AFMU+1U+1X) (urine).
In stratified analysis, a statistical significance within the caffeinated group was observed for the change in systolic BP in the stratum of CYP1A2 polymorphism with daily caffeine consumption ≤90 mg/day: change in systolic BP in the CYP1A2rs762551 CC group (mean ± SD = 11.8 ± 5.9) was higher than that in the AA/CA group (4.1 ± 5.5).
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).
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).
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.
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.
Correlations were not seen between PhIP-Alb adduct levels and PhIP intake levels (P = 0.76), the amount of PhIP accrued in hair (P = 0.13), the amounts of N-oxidized urinary metabolites of PhIP (P = 0.66) or caffeineCYP1A2 activity (P = 0.55), a key enzyme involved in the bioactivation of PhIP.
The pharmacokinetics of caffeine are highly variable among individuals due to a polymorphism at the level of the CYP1A2 isoform of cytochrome P450, which metabolizes 95% of the caffeine ingested.
Activity of five isozymes was estimated by comparing plasma pharmacokinetics of substrates and their metabolites (caffeine/paraxanthine for CYP1A2, losartan/E-3174 for CYP2C11, omeprazole/5-hydroxyl omeprazole for CYP2C6, dextromethorphan/dextrophan for CYP2D2 and midazolam/1-hydroxyl midazolam for CYP3A1/2) between control and drug treatment groups.