La caféine, données de base et facteurs capables de les modifier

Abstract

La quantité de caféine inaltérée dans l'urine est approximativement de 1% de la dose administrée. La concentration urinaire de caféine dépend du volume d'urine excrété et de la dose administrée. Dans le contrôle antidopage, le Comité Olympique International considère qu'un échantillon est positif à la caféine si sa concentration en urine est égale ou supérieure à 12 μ g·ml −1 . Le métabolisme et l'excrétion urinaire de la caféine subit des variations qualitatives et quantitatives sous l'influence de nombreux facteurs. Un exemple particulièrement important est celui de l'interaction pharmacologique avec d'autres xénobiotiques. Parmi ceux-ci la furafylline, l'idrocilamide et les antibiotiques du groupe des quinolones comme l'acide pipémidique sont capables, entre autres, de modifier les données de base de la caféine. Les interactions sur le métabolisme et la pharmacocinétique de la caféine doivent être considérées. Cependant pour atteindre une concentration sanctionnable de caféine dans l'urine, il faut que la dose administrée soit très importante. The quantity of unchanged caffeine in the urine is about 1% of the administered dose. The concentration in urine is also dependent on urinary flow rate. Any value above 12 μg/ml is considered representative of a non authorized caffeine ingestion according to the International Olympic Committee. Caffeine is completely absorbed after oral administration. Kinetics are linear in the dose range 1 to 10 mg/kg. Its half-life is 2 to 6 h in the adult and its distribution volume is 0.6 l/kg. A significant correlation ( n =14, P <0.001) has been found between plasmatic and salivary caffeine concentrations. A close relationship exists between ingested dose and caffeine concentration in urine. A high dose is required to reach non authorized levels. Maximal caffeine concentrations of 10.64±2.89 μg/ml have been quantified in volunteers ( n =9) after the ingestion of 1 g of caffeine. Hepatic metabolism (cytochrome P-448) is the main factor which is responsible for caffeine elimination (N3-demethylation). Both the metabolic and the renal clearance of caffeine may be altered by different factors. Some of these are age, pregnancy, enzymatic induction in smokers and certain drug interactions, such as those caused by furafylline and idrocilamide. Concentrations in plasma up to 10 to 40 μg/ml as a result of furafylline treatment have been detected even after abnormal caffeine intake. When caffeine (165 mg) was administered together with idrocilamide (daily dose 1200 mg), caffeine half-life was increased 9-fold and its renal excretion as unchanged drug raised by the order of 150 to 400%. The effect of quinolone antibiotics on the metabolism and excretion of xanthines has also been recently described. Undesirable side effects were reported in patients treated with theophylline and either enoxacin or pipemidic acid. A single blind, randomized clinical trial in 6 healthy volunteers taking pipemidic acid, norfloxacin or placebo was designed to study the effects on caffeine disposition. Both quinolones caused and increase in areas under the plasma concentration-time curves and a reduction in caffeine plasma clearance. Pipemidic acid produced a 346% increase in caffeine half-life. A metabolic inhibition appears to be the factor responsible due to the absence of difference in volume of distribution, renal elimination of the unchanged drug and absorption as compared to placebo. Potential effects of other compounds or situations on the metabolism and pharmacokinetics of caffeine must thus be considered. In any event, however, the cut-off level cited above is only reached after dosage a high caffeine.