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Title 

Effect of grapefruit juice on CYP1A2 dependent metabolism of caffeine in Korean

 

한국인에서 CYP1A2 의존성 caffeine 대사에 대한 자몽과즙의 억제효과

Authors 

Ju-Hee KangHyung-Keun RohYil-Seob LeeWoon-Gye ChungKyung-Hoon LeeHwan Mook KimYoung-Nam Cha

Issue Date 

1997

Citation 

Korean Journal of Clinical Pharmacology Therapeutics, vol. 5, no. 1, pp. 26-34

Keywords 

CaffeineGrapefruit juiceCytochrome P450CYP1A2Korean

Abstract 

Background: As caffeine is specifically N3-demethylated by CYP1A2, caffeine has been used as a metabolic probe to determine the relative CYP1A2 activity in human. Grapefruit juice has been demonstrated to inhibit mammalian cytochrome P450 enzymes like CYP3A4. Thus, the objective of this study was to determine whether the grapefruit juice will inhibit the CYP1A2 activity in unrelated healthy Korean subjects. Method: Volunteers(47 subjects) refraining from methylxanthine-containing foods or beverages were given a cup of coffee (110mg caffeine) at 8 a.m.. They voided urine at 12 a.m. and provided 1 hr urine sample at 1 p.m.. On the second day, the volunteers were given 500ml of grapefruit juice at 7 a.m. and at 8 a.m., they were given 1 cup of coffee. At 9 a.m. and 11 a.m., they were given 500ml of grapefruit juice again. Again, the volunteers voided urine at 12 a.m. and provided the 1 hr urine sample at 1 p.m. The caffeine metabolites present in the urine samples from both days were analyzed with HPLC. The relative CYP1A2 activities in each individual were calculated by taking the molar concentration ratio of [paraxanthine + 1,7-dimethylurate]/[caffeine]. Results: The basal CYP1A2 activity for all volunteers was 15.3±7.7 and after taking the grapefruit juice, the CYP1A2 activity was decreased significantly to 10.3±6.2 (Wilcoxon signed-rank test, p<0.0001). Upon intake of the grapefruit juice, the CYP1A2 activity was decreased in 39 volunteers but the CYP1A2 activity in 8 was increase slightly. The CYP1A2 activities of smokers either before or after the grapefruit juice intake were higher (Mann-Whitney U test, p<0.005) and thus, the induction of enzyme activity by cigarette smoking was confirmed. There were no significant differences in the fraction of CYP1A2 inhibition between the nonsmokers and smokers, and the fraction of CYP1A2 activity inhibition had no significant relationship with the basal activity. Conclusion : Intake of grapefruit juice will inhibit the CYP1A2 activity in man and will interfere with the metabolism of clinically useful drugs which are metabolized by CYP1A2. Therefore, in persons whose CYP1A2 activity is severely inhibited by grapefruit juice, taking drugs metabolized by CYP1A2 together with grapefruit juice could bring unexpected drug toxicity. Conversely, as the CYP1A2 is known to ha involved in metabolic activation of procarcinogens belonging to aromatic amines (in cigarette) or heterocyclic amines (in broiled meats), taking grapefruit juice would lower the cancer susceptibility.

ISSN 

1225-5467

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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