Caffeine, biotransformation

Krul C, Hageman G (1998) Analysis of urinary caffeine metabolites to assess biotransformation enzyme activities by reversed-phase high-performance liquid chromatography, J ChromatogrB Biomed Sci Appl 709(l) 27-34... 

For most drugs, oxidative biotransformation is performed primarily by the mixed-function oxidase enzyme system, which is present predominantly in the smooth endoplasmic reticulum of the liver. This system comprises (1) the enzyme NADPH cytochrome P450 reductase (2) cytochrome P450, a family of heme-containing proteins that catalyze a variety of oxidative and reductive reactions and (3) a phospholipid bilayer that facilitates interaction between the two proteins. Important exceptions to this rule are ethyl alcohol and caffeine, which are oxidatively metabolized by enzymes primarily present in the soluble, cytosolic fraction of the liver. 

The pharmacokinetics of caffeine is greatly altered by concomitant administration of the myorelaxant, idrocilamide, which inhibits the biotransformation of caffeine and prolongs its half-life nine-fold (SEDA-5, 7). Consequently, when idrocilamide is prescribed, partial... 

Other oxidative enzymes, though certainly important in the biotransformation of some drugs (e.g., xanthine oxidase contributes to the overall metabolism of substances such as caffeine and theophylline), are not responsible for the metabolism for very many drugs compared to the GYP enzymes. 

C. Kudla, Y. Keita et al. (1992). Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Biochem. Pharmacol. 43, 225-235. 

Campbell ME, Grant DM, Inaba T, Kalow W.Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible C5 tochrome(s) P-450 in human liver microsomes. Drug Metab Dispos 1987 15 237-249. 

Harder S, Staib AH, Beer C, Papenburg A, Stifle W, Shah PM. 4-Quinolones inhibit biotransformation of caffeine. EurJ Clin Pharmacol (1988) 35, 651-6. 

Caffeine is rapidly absorbed and distributed in all body tissues and fluids, including CNS, fetal tissues, and breast milk. Elimination is by biotransformation in liver and renal excretion of metabolites. Some authors beheve that caffeine alone might have analge-264 sic properties for specific types of pain in humans and... 

Important kinetic differences and variations in the quantitative as well as qualitative metabolic profiles have been shown between species, thus making extrapolation from one species to another very difficult. All of the metabolic transformations include multiple and separate pathways with demethylation to dimethyl- and monomethylxanthines, formation of dimethyl- and monomethylurates, and ring opening yielding substituted diaminouracils (Figure 2). The reverse biotransformation of theophylline to caffeine is demonstrated not only in infants but also in adults. 

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