Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat.
Journal Title: Pharmacological Reports - Year 2008, Vol 60, Issue 6
Abstract
The current knowledge on the involvement of cytochrome P450 (P450, CYP) isoforms in the metabolism of caffeine in rat and human liver is reviewed. Attention is also paid to species- and concentration-dependent metabolism of caffeine. Finally, we discuss the P450-mediated metabolism of caffeine in relation to coffee addiction and drug interactions. Due to its safety, favorable pharmacokinetic properties, and P450 isoform-selective metabolism, caffeine has great potential as a metabolic marker substance in both humans and rats, and as a more universal metabolic tool in the latter species. However, the qualitative and relative quantitative contribution of P450 isoforms to the metabolism of caffeine is species- and concentration-dependent. While 3-N-demethylation is quantitatively the main oxidation pathway in human, 8-hydroxylation is the dominant metabolic pathway in rat. Both of these main reactions in the two species are specifically catalyzed by CYP1A2. Caffeine may be applied as a marker substance for assessing the activity of CYP1A2 in human and rat liver, but by using different reactions: 3-N-demethylation in humans and C-8-hydroxylation in rats. In addition, caffeine can be used to preliminarily and simultaneously estimate CYP2C activity in rat liver using 7-N-demethylation as a marker reaction. On the other hand, CYP3A4-catalyzed 8-hydroxylation in humans is not sufficiently isoform-specific to mark the activity of CYP3A4. Caffeine pharmacokinetics may be changed by drugs affecting the activity of CYP1A2 (human and rat) or CYP2C (rat), e.g. via autoinduction or by treatment with certain antidepressants or neuroleptics. Therefore, patients taking caffeine-containing medicine or coffee drinkers taking drugs that interact with CYP1A2 may require proper dosage adjustments upon caffeine ingestion and cessation.
Authors and Affiliations
Marta Kot, Władysława Daniel
NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice.
It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was...
Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment.
Increasing numbers of studies indicate that free radicals and their derivatives play a role in some neuropsychiatric disorders, such as depression. The aim of this study was to investigate the activities of antioxidant e...
Preserved coronary arteriolar dilatation in patients with type 2 diabetes mellitus: Implications for reactive oxygen species.
Type 2 diabetes mellitus is associated with clustering of cardiovascular risk factors that may greatly increase individuals' risk of developing coronary artery disease. Type 2 diabetes is believed to impair coronary func...
Comparative study of the anti-edematogenic effects of anethole and estragole.
Background: Anethole and estragole are monoterpene position isomers and constituents of essential oils from aromatic plants and were used in this study with the aim of analyzing their anti-inflammatory activity. Methods:...
Influence of enalapril, quinapril and losartan on lipopolysaccharide (LPS)-induced serum concentrations of TNF-alpha, IL-1beta, IL-6 in spontaneously hypertensive rats (SHR).
Immunopharmacological studies of drugs used in cardiovascular diseases provide new data concerning their modulating effect on the levels of proinflammatory cytokines, chemokines and adhesion molecules. Therefore, we have...