Pharmacokinetics of caffeine

Beach, C. A., Mays, D. C., Sterman, B. M. and Gerber, N. 1985. Metabolism, distribution, seminal excretion and pharmacokinetics of caffeine in the rabbit. Journal of Pharmacology and Experimental Therapy, 233 18-23. 

Knutti R, Rothweiler H, Schlatter C Effect of pregnancy on the pharmacokinetics of caffeine. Eur J Clin Pharmacol 21 121-126, 1981... 

Cheng, W.S.C., Murphy, T.L., Smith, M.T., Cooksiey, W.G.E., Haiiiday, J.W., Powell, L.W. Dose-dependent pharmacokinetics of caffeine in humans relevance as a test of quantitative liver functions. Clin. Pharmacol. Ther. 1990 47 516-524... 

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... 

Wahllander A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur I Clin Pharmacol 1989 37(3) 279-83. 

Nix DE, Zelenitsky SA, Symonds WT, Spivey JM, Norman A. The effect of fluconazole on tile pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther (1992) 51,183. 

Echinacea appears to have a variable effect on the pharmacokinetics of caffeine. 

There are conflicting results from studies of the interaction of kava and caffeine. It appears that kava is unlikely to affect the pharmacokinetics of caffeine, although further study is required to confirm this. 

The effects of various quinolones on the pharmacokinetics of caffeine " are summarised in Table 33.3 , (p.l 167). In one study ciprofloxacin and fleroxacin increased caffeine levels more in women than men, but this difference in effect was not significant when the results were normalised for body weight. ... 

LeBel M, Teng R, Dogolo LC, Willavize S, Friedman HL, Vincent J. The influence of steady-state trovafloxacin on the steady-state pharmacokinetics of caffeine in healthy... 

Tsai T-H, Chang C-H, Lin L-C. Effects of Evodia rutaecarpa and rataecarpine on the pharmacokinetics of caffeine in rats. Planta Med 2005 71 640-5. 

Caffeine pharmacokinetics are nonlinear. For example, when comparing a 500 mg dose to a 250 mg dose, the clearance is reduced and elimination half-life is prolonged with the higher dose (Kaplan et al. 1997). Thus, larger doses prolong the action of the drug. Active metabolites of caffeine are paraxanthine, and to a lesser degree, theobromine, and theophylline. Urinary metabolites are I-methylxanthine, l-methyluric acid, and an acetylated uracil derivative. 

Kaplan GB, Greenblatt DJ, Ehrenberg BL, Goddard JE, Cotreau MM, Harmatz JS, Shader RI. (1997). Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. J Clin Pharmacol. 37(8) 693-703. 

As shown below, theophylline is 1,3-dimethylxanthine theobromine is 3,7-dimethylxanthine and caffeine is 1,3,7-trimethylxanthine. A theophylline preparation commonly used for therapeutic purposes is aminophylline, a theophylline-ethylenediamine complex. A synthetic analog of theophylline (dyphylline) is both less potent and shorter-acting than theophylline. The pharmacokinetics of theophylline are discussed below (see Clinical Use of Methylxanthines). The metabolic products, partially demethylated xanthines (not uric acid), are excreted in the urine. 

Ginsberg G, Hattis D, Russ A, Sonawane B (2004c) Physiologically based pharmacokinetic (PBPK) modeling of caffeine and theophylline in neonates and adults Implications for assessing children s risks from environmental agents. J Toxicol Environ Health A, 67(4) 297-329. 

Klockowski PM. Effect of venlafaxine on CYPlA2-depen-dent pharmacokinetics and metabolism of caffeine. J Clin Pharmacol 1999 39(3) 252-9. 

Thithapandha A. Effect of caffeine on the bioavaUability and pharmacokinetics of aspirin. J Med Assoc Thai 1989 72(10) 562-6. 

Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Chn Pharmacol 2000 49(l) 59-63. 

In 24 healthy volunteers, 12 men and 12 women, the women had significantly different caffeine pharmacokinetics in the presence of ciprofloxacin and fleroxacin compared with the men (132). There were also significant differences between the sexes in the pharmacokinetics of ciprofloxacin and fleroxacin in the presence of caffeine. The differences were in part due to different body weights. 

Pharmacokinetic and pharmacodynamic interactions between caffeine 250 mg and phenylpropanolamine 25 mg have been investigated in six healthy subjects in a double-blind, placebo-controlled study. Coadministration of caffeine and phenylpropanolamine produced an additive increase in blood pressure, not attributable to a pharmacokinetic interaction and despite the fact that phenylpropanolamine attenuated the responses of adrenaline and renin to caffeine (17). 

Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther 1991 49(3) 248-55. 

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