A fluvoxamine-caffeine interaction study
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
A fluvoxamine-caffeine interaction study. / Jeppesen, U; Loft, S; Poulsen, H E; Brśen, K.
In: Pharmacogenetics and Genomics, Vol. 6, No. 3, 06.1996, p. 213-22.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A fluvoxamine-caffeine interaction study
AU - Jeppesen, U
AU - Loft, S
AU - Poulsen, H E
AU - Brśen, K
PY - 1996/6
Y1 - 1996/6
N2 - The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between fluvoxamine and caffeine. The study was carried out as a randomized, in vivo, cross-over study including eight healthy volunteers. In Period A of the study, each subject took 200 mg caffeine orally, and in Period B, the subjects took fluvoxamine 50 mg per day for 4 days and 100 mg per day for 8 days. On day 8 in Period B, the subjects again ingested 200 mg caffeine. After caffeine intake, blood and urine were sampled at regular intervals. Caffeine and its three primary demethylated metabolites, paraxanthine, theobromine and theophylline in plasma and the same four compounds plus 11 more metabolites in urine were assayed by HPLC. During fluvoxamine, the median of the total clearance of caffeine decreased from 107 ml min-1 to 21 ml min-1 and the half-life increased from 5 to 31 h. The N3-demethylation clearance of caffeine to paraxanthine decreased from 46 to 9 ml min-1; the N1- and N7-demethylation clearances decreased from 21 to 9 ml min-1 and from 14 to 6 ml min-1, respectively. The results confirm that CYP1A2 is the main enzyme catalysing the biotransformation of caffeine, in particular the N3-demethylation and partly the N1- and N7-demethylation. The results indicate that intake of caffeine during fluvoxamine treatment may lead to caffeine intoxication. Finally, our study provides additional evidence that fluvoxamine can be used to probe CYP1A2 in drug metabolism.
AB - The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between fluvoxamine and caffeine. The study was carried out as a randomized, in vivo, cross-over study including eight healthy volunteers. In Period A of the study, each subject took 200 mg caffeine orally, and in Period B, the subjects took fluvoxamine 50 mg per day for 4 days and 100 mg per day for 8 days. On day 8 in Period B, the subjects again ingested 200 mg caffeine. After caffeine intake, blood and urine were sampled at regular intervals. Caffeine and its three primary demethylated metabolites, paraxanthine, theobromine and theophylline in plasma and the same four compounds plus 11 more metabolites in urine were assayed by HPLC. During fluvoxamine, the median of the total clearance of caffeine decreased from 107 ml min-1 to 21 ml min-1 and the half-life increased from 5 to 31 h. The N3-demethylation clearance of caffeine to paraxanthine decreased from 46 to 9 ml min-1; the N1- and N7-demethylation clearances decreased from 21 to 9 ml min-1 and from 14 to 6 ml min-1, respectively. The results confirm that CYP1A2 is the main enzyme catalysing the biotransformation of caffeine, in particular the N3-demethylation and partly the N1- and N7-demethylation. The results indicate that intake of caffeine during fluvoxamine treatment may lead to caffeine intoxication. Finally, our study provides additional evidence that fluvoxamine can be used to probe CYP1A2 in drug metabolism.
KW - Adult
KW - Biotransformation
KW - Caffeine
KW - Chromatography, High Pressure Liquid
KW - Cytochrome P-450 CYP1A2
KW - Cytochrome P-450 CYP1A2 Inhibitors
KW - Drug Interactions
KW - Fluvoxamine
KW - Half-Life
KW - Humans
KW - Methylation
KW - Reference Values
KW - Serotonin Uptake Inhibitors
M3 - Journal article
C2 - 8807660
VL - 6
SP - 213
EP - 222
JO - Pharmacogenetics
JF - Pharmacogenetics
SN - 1744-6872
IS - 3
ER -
ID: 156510370