PMID- 10584979
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20151119
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 37
IP  - 11
DP  - 1999 Nov
TI  - Omeprazole weakly inhibits CYP1A2 activity in man.
PG  - 567-74
AB  - BACKGROUND AND OBJECTIVES: Omeprazole is an inducer of human cytochrome P450 1A 
      (CYP1A) enzymes, but shows inhibitory effects on CYP2C19 and CYP3A4. In this 
      study, a potential inhibitory effect of omeprazole on caffeine metabolism, a 
      validated CYP1A2 marker, was examined. METHODS: A randomized, balanced crossover 
      single-dose study was conducted in 16 healthy volunteers comprising 12 extensive 
      (EM) and 4 poor metabolizers (PM) for CYP2C19. All volunteers received a 40 mg 
      omeprazole dose or placebo 0.5 h prior to caffeine 3 mg/kg body weight. Six EMs 
      were re-tested with 80 mg of omeprazole. In vitro, effects of omeprazole on 
      caffeine N3-demethylation were determined in human liver microsomes. RESULTS: In 
      vivo, non-parametric point estimates (90% confidence intervals) for the ratios of 
      caffeine pharmacokinetics with/without co-administration of the 40 mg omeprazole 
      dose were: AUC 1.08 (1.04 - 1.13), MRT 1.09 (0.99 - 1.19), and plasma ratio of 
      paraxanthine/caffeine 6 h post-dose 0.91 (0.80 - 1.00). Inhibition of caffeine 
      N3-demethylation by omeprazole was slightly more pronounced in PM than in EM of 
      CYP2C19. Estimates for the 80 mg omeprazole dose were: AUC 1.12 (1.05 -1.18), MRT 
      1.18 (1.07 - 1.30), and paraxanthine/caffeine ratio 0.83 (0.74 -0.94). In vitro, 
      omeprazole was mainly a competitive CYP1A2 inhibitor with K(i) values of around 
      150 microM. CONCLUSIONS: Omeprazole exerts a concentration-dependent inhibition 
      of CYP1A2 activity in man. However, even after single oral doses up to 80 mg, 
      this effect is weak and without clinical relevance.
FAU - Rost, K L
AU  - Rost KL
AD  - PAREXEL Institute of Clinical Pharmacology, Klinikum Westend, Berlin, Germany.
FAU - Fuhr, U
AU  - Fuhr U
FAU - Thomsen, T
AU  - Thomsen T
FAU - Zaigler, M
AU  - Zaigler M
FAU - Brockmoller, J
AU  - Brockmoller J
FAU - Bohnemeier, H
AU  - Bohnemeier H
FAU - Roots, I
AU  - Roots I
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Biomarkers)
RN  - 0 (Cytochrome P-450 CYP1A2 Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 3G6A5W338E (Caffeine)
RN  - C137DTR5RG (Theophylline)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - KG60484QX9 (Omeprazole)
RN  - Q3565Y41V7 (1,7-dimethylxanthine)
SB  - IM
MH  - Adult
MH  - Binding, Competitive
MH  - Biomarkers/blood
MH  - Caffeine/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Cytochrome P-450 CYP1A2/*metabolism
MH  - *Cytochrome P-450 CYP1A2 Inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme Inhibitors/*administration & dosage
MH  - Female
MH  - Humans
MH  - In Vitro Techniques
MH  - Male
MH  - Microsomes, Liver/*drug effects/metabolism
MH  - Omeprazole/*administration & dosage
MH  - Single-Blind Method
MH  - Theophylline/blood
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 1999 Nov;37(11):567-74.