A fluvoxamine-caffeine interaction study

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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 journalJournal articleResearchpeer-review

Harvard

Jeppesen, U, Loft, S, Poulsen, HE & Brśen, K 1996, 'A fluvoxamine-caffeine interaction study', Pharmacogenetics and Genomics, vol. 6, no. 3, pp. 213-22.

APA

Jeppesen, U., Loft, S., Poulsen, H. E., & Brśen, K. (1996). A fluvoxamine-caffeine interaction study. Pharmacogenetics and Genomics, 6(3), 213-22.

Vancouver

Jeppesen U, Loft S, Poulsen HE, Brśen K. A fluvoxamine-caffeine interaction study. Pharmacogenetics and Genomics. 1996 Jun;6(3):213-22.

Author

Jeppesen, U ; Loft, S ; Poulsen, H E ; Brśen, K. / A fluvoxamine-caffeine interaction study. In: Pharmacogenetics and Genomics. 1996 ; Vol. 6, No. 3. pp. 213-22.

Bibtex

@article{5593edb594ff43b5979976d645c173a6,
title = "A fluvoxamine-caffeine interaction study",
abstract = "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.",
keywords = "Adult, Biotransformation, Caffeine, Chromatography, High Pressure Liquid, Cytochrome P-450 CYP1A2, Cytochrome P-450 CYP1A2 Inhibitors, Drug Interactions, Fluvoxamine, Half-Life, Humans, Methylation, Reference Values, Serotonin Uptake Inhibitors",
author = "U Jeppesen and S Loft and Poulsen, {H E} and K Brśen",
year = "1996",
month = "6",
language = "English",
volume = "6",
pages = "213--22",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams & Wilkins",
number = "3",

}

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

VL - 6

SP - 213

EP - 222

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 3

ER -

ID: 156510370