Interspecies Comparison of Caffeine Disposition

Abstract

In line with its physiochemical characteristics (undissociated weak electrolyte at physiological pH, pK_a 1 and 14, partition coefficient 0.85 (Gaspari et al. 1983; Bonati et al. 1982 a), caffeine is rapidly and completely absorbed from the gastrointestinal tract after oral administration (Axelrod and Reichenthal 1953; Bonati et al. 1982 b, Blanchard and Sawers 1983 a). In animals and man no significant first-pass effect occurs after oral caffeine (Aldridge, et al. 1977). Although different absorption rates have been estimated for different species, mean values of the rate constant of absorption (k _abs ) range from 4 to 6h^-1; plasma peal levels are reached within 30–120 min of dosing in animals and man (Latini et al. 1978; Garattini et al. 1979; Bonati et al. 1982 b). Lower k _abs values were reported after ingestion of caffeine in a soft drink than after coffee and caffeine aqueous solutions (Marks and Kelly 1973; Bonati et al. 1982 b), suggesting that the characteristics (volume, pH, composition) of sources in which caffeine is dissvolved may influence its absorption rate. A tendency for the absorption rate to rise with increasing doses of caffeine was described (Garattini et al. 1980b; Bonati et al. 1982b). The absorption rate was lower after in-tramusuclar than oral dosing, indicating that solubility at site of administration may be another variable to consider (Sant’Ambrogio et al. 1964).