Bioavailability Caffeine

Kamimori GH, Karyekar CS, Otterstetter R, Cox DS, Balldn TJ, Belenky GL, and Eddington ND (2002) The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Int. J. Pharm. 234 159-167. 

Gum formulations containing caffeine showed rapid release and absorption of the agent with comparable bioavailability to the capsule form [57], Various gum formulations with vitamin C [56], diphenhydramine [58], methadone [59], and verapamil [60] have been developed and tested. 

Disposition in the Body. Rapidly absorbed after oral administration bioavailability almost 100%. Metabolic reactions include V-demethylation and oxidation to uric acid derivatives. About 85% of a dose is excreted in the urine in 48 hours with up to 40% of the dose as 1-methyluric acid, 10 to 15% as 1-methylxanthine and up to 35% as 5-acetylamino-6-formylamino-3-methyluracil and 5-acetylamino-6-amino-3-methyluracil other metabolites excreted in the urine include theophylline, 1,7-dimethylxanthine (paraxanthine), 7-methylxanthine, and 1,3-dimethyluric acid. Less than 10% is excreted in the urine as unchanged drug. The extent of V-acetylation is genetically determined. Caffeine, theophylline, theobromine, and paraxanthine are found in plasma from dietary sources especially coffee, tea and cocoa. An average cup of coffee or tea contains approximately 100 mg of caffeine. 

Despite the fact that a plethora of dietary factors could, and will, affect the absorption characteristics of phytochemicals, this area has not been systematically explored. One reason might be the complexity of dietary factors and their interactions that could affect absorption. A nonexhaustive list would include the volume and composition of the food consumed, pH, caloric density, viscosity, nutrients (carbohydrates, protein, fat, fibers), alcohol, caffeine, and the presence of other phytochemicals. Such dietary factors affect the functional status, motility, and acidity of the gastrointestinal tract in a complex manner and modify the physicochemical properties, formulation, and dissolution characteristics of the compound of interest. Calcium in dairy products, for example, has the potential to chelate tetracyclines and fluoroquinolones and, thereby, reduce their bioavailability and biological activity [31]. 

Caffeine modestly increases the bioavailability, rate of absorption and plasma levels of aspirin. Adding caffeine to diclofenac may improve its efficacy in the treatment of migraine. 

Tukker JJ, Sitsen JMA, Gusdorf CF. Bioavailability of paracetamol after oral administration to healthy volunteera. Influence of caffeine on rate and extent of absorption. Pharm Weeldyl (Sci) (1986) 8,239-43. 

The clearance of caffeine is considerably reduced by fluvoxamine. An increase in the stimulant and adverse effects of caffeine would be expected, however this was not demonstrated in one study. Caffeine may cause a reduction in the bioavailability of fluvoxamine. 

Drug-food interactions A systematic review evaluating interactions between CBZ and food [60 ] found that caffeine decreases oral bioavailability and impairs the anticonvulsant efficacy of CBZ in both human and animal studies. Grapefruit, kinnow, pomegranate, and star fruit juices cause an increase in the oral bioavailability of CBZ through inhibition of enteric CYP3A4 activity. 

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