Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects

Sato, Junichi; Nakata, Hiromasa; Owada, Eiji; Kikuta, Takahiro; Umetsu, Masao; Ito, Keiji

doi:10.1007/bf00271376

Cited by 14 publications

(4 citation statements)

References 18 publications

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“…The greatest effect was observed in patients who were heavy smokers (40 cigarettes per day) . Concomitant caffeine and theophylline ingestion also reduced the elimination of both compounds …”

Section: Medicinal Chemistry Of Caffeinementioning

confidence: 94%

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The Medicinal Chemistry of Caffeine

2021

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The purine alkaloid caffeine is the most widely consumed psychostimulant drug in the world and has multiple beneficial pharmacological activities, for example, in neurodegenerative diseases. However, despite being an extensively studied bioactive natural product, the mechanistic understanding of caffeine’s pharmacological effects is incomplete. While several molecular targets of caffeine such as adenosine receptors and phosphodiesterases have been known for decades and inspired numerous medicinal chemistry programs, new protein interactions of the xanthine are continuously discovered providing potentially improved pharmacological understanding and a molecular basis for future medicinal chemistry. In this Perspective, we gather knowledge on the confirmed protein interactions, structure activity relationship, and chemical biology of caffeine on well-known and upcoming targets. The diversity of caffeine’s molecular activities on receptors and enzymes, many of which are abundant in the CNS, indicates a complex interplay of several mechanisms contributing to neuroprotective effects and highlights new targets as attractive subjects for drug discovery.

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Section: Medicinal Chemistry Of Caffeinementioning

confidence: 94%

“…76 Concomitant caffeine and theophylline ingestion also reduced the elimination of both compounds. 77 2.2. Molecular Activities of Caffeine.…”

Section: Medicinal Chemistry Of Caffeinementioning

confidence: 99%

The Medicinal Chemistry of Caffeine

2021

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“…It has been reported that caffeine consumption might influence the pharmacokinetics of drugs which are substrates of CYP1A2 (Sato et al 1993; Vainer & Chouinard 1994) and, accordingly, our recent data indicated that caffeine increases the bioavailability of melatonin by 120% due to inhibition of melatonin first‐pass metabolism without significant effect on the elimination half‐life (Härter et al 2003). Thus, dietary caffeine intake could be a potential confounder when melatonin is used for CYP1A2 phenotyping.…”

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confidence: 99%

Effect of Caffeine Intake 12 or 24 Hours Prior to Melatonin Intake and CYP1A21F* Polymorphism on CYP1A2 Phenotyping by Melatonin

Härtter

Korhonen

Lundgren

et al. 2006

Basic Clin Pharma Tox

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Earlier evidence suggests that melatonin is almost exclusively metabolised by CYP1A2 and could serve as a probe drug for CYP1A2 phenotyping. However, caffeine inhibits the metabolism of melatonin by CYP1A2 and dietary caffeine could be a potential confounder for the measurement of CYP1A2 activity with melatonin. We undertook a 3-phase cross-over study in 12 healthy volunteers to examine whether caffeine (200 mg single dose), taken 12 hr or 24 hr prior to melatonin intake, would affect the results of CYP1A2 phenotyping results as assessed by a spot sample melatonin concentration 1.5 hr after intake of 6 mg of melatonin orally. In addition we examined the influence of the CYP1A2*1F polymorphism on the phenotyping results by combining the present material with another 12 persons from a previous study. Caffeine, co-administered 12 or 24 hr prior to melatonin intake, did not have any significant effect on the 1.5 hr melatonin concentration (PΩ0.086 for ANOVA), but in two volunteers about 4 times increase in melatonin concentration was observed after caffeine intake 12 hr (but not 24 hr) before phenotyping with melatonin. Also, individuals homozygous for the CYP1A2*1A allele had clearly higher 1.5 hr melatonin concentration compared with the *1F/*1F or the *1F/*1A genotypes. Abstinence from caffeine for 24 hr prior to melatonin intake should be enough to overcome the possible confounding effect of caffeine on the CYP1A2 phenotyping with melatonin. Also, melatonin may be a sensitive probe to detect phenotypic differences with regard to CYP1A2*1F polymorphism. Melatonin might be, thus, advantageous for CYP1A2 phenotyping compared to the standard probe caffeine.

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“…Inhibitors of CYP1A2 increase serum caffeine concentration (Carrillo & Benítez 2000), and caffeine itself may act as a CYP1A2 inhibitor. In an open cross‐over trial, caffeine‐containing instant coffee at 2 to 7 cups per day reduced the clearance of CYP1A2 substrate theophylline by 23% (Sato et al 1993).…”

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confidence: 99%

Effect of Caffeine‐Containing versus Decaffeinated Coffee on Serum Clozapine Concentrations in Hospitalised Patients

Raaska

Raitasuo

Laitila

et al. 2004

Basic Clin Pharma Tox

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Clozapine and caffeine are metabolised mainly by the cytochrome P4501A2 (CYP1A2) enzyme. Studies suggest that caffeine in coffee inhibits clozapine metabolism and increases serum clozapine concentrations. Our objective was to study whether coffee in the amounts usually consumed has an effect on steady-state serum clozapine concentrations. A randomised placebo-controlled cross-over design with two phases was used. Twelve hospitalised clozapine-using patients volunteered in the study where, after one-week run-in period, either caffeine-containing or decaffeinated instant coffee was available ad libitum for seven days. Serum concentrations of clozapine, N-desmethylclozapine, clozapine-N-oxide, caffeine, paraxanthine and C-reactive protein were measured after run-in period and on days 4 and 8 of the following study phases. Two patients were excluded from the statistical analysis because of non-compliance based on serum caffeine and paraxanthine determinations. In six fully compliant patients caffeine-containing coffee increased the mean serum trough concentration of clozapine by 26% (non-significant (NS), 95% CI ª3% to π54%, PΩ0.07), N-desmethylclozapine by 6% (95% CI 1% to 12%, PΩ0.03), and clozapine-N-oxide by 7% (NS, 95% CI ª6% to π20%, PΩ0.22). The ratio of N-desmethylclozapine/clozapine decreased by 13% (NS, 95% CI ª1% to π27%, PΩ0.06) and that of clozapine-N-oxide/ clozapine by 7% (NS, 95% CI ª5% to π17%, PΩ0.19). In the analysis of combined data (including day 4 data of the four patients compliant up to that point) serum trough concentration of clozapine was 20% (95% CI 3% to 37% to PΩ 0.03) higher, and that of N-desmethylclozapine 7% (95% CI 2% to 13%, PΩ0.02) higher during the caffeine phase than during the decaffeinated phase. We conclude that the effect of instant coffee drinking on serum clozapine concentrations is of minor clinical relevance in most of the patients, but some individuals may be more sensitive to this interaction due e.g. to genetic factors. The increase in serum clozapine concentration was most likely due to the inhibition of the CYP1A2 enzyme by caffeine.

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Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects

Cited by 14 publications

References 18 publications

The Medicinal Chemistry of Caffeine

The Medicinal Chemistry of Caffeine

Effect of Caffeine Intake 12 or 24 Hours Prior to Melatonin Intake and CYP1A21F* Polymorphism on CYP1A2 Phenotyping by Melatonin

Effect of Caffeine‐Containing versus Decaffeinated Coffee on Serum Clozapine Concentrations in Hospitalised Patients

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Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects

Cited by 14 publications

References 18 publications

The Medicinal Chemistry of Caffeine

The Medicinal Chemistry of Caffeine

Effect of Caffeine Intake 12 or 24 Hours Prior to Melatonin Intake and CYP1A2*1F Polymorphism on CYP1A2 Phenotyping by Melatonin

Effect of Caffeine‐Containing versus Decaffeinated Coffee on Serum Clozapine Concentrations in Hospitalised Patients

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Effect of Caffeine Intake 12 or 24 Hours Prior to Melatonin Intake and CYP1A21F* Polymorphism on CYP1A2 Phenotyping by Melatonin