Effect of Complex Formation on Drug Absorption VII: Effect of Complexation and Self-Association on the Absorption of Caffeine

• Published in: Journal of pharmaceutical sciences 1968-08, Vol.57 (8), p.1335-1341
• Main Authors: Reuning, Richard H., Levy, Gerhard
• Format: Article
• Language: English
• Subjects: Animals; Benzoates - metabolism; Biological Transport, Active; Caffeine - administration & dosage; Caffeine complexes-increased partition coefficients; Drug absorption-complex formation effect; Drug Synergism; Everted intestine-experimental technique; Gastric absorption rate-in situ technique; Gastric Mucosa - metabolism; Intestinal Absorption; Rats; Salicylates - metabolism; Salicylic acid retardation-caffeine transfer; Self-association-caffeine; Spectrophotometry; Stomach - physiology; Time Factors; UV spectrophotometry-analysis
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600570812

The effect of the formation of caffeine complexes having a higher apparent lipoidaqueous partition coefficient than caffeine itself on the absorption of this drug from the rat stomach was investigated. In one such system, caffeine-salicylic acid, the salicylic acid actually decreased the absorption of caffeine due to an effect of the former on the gastric mucosa. In another such system, caffeine-p-hydroxybenzoic acid, the p-hydroxybenzoic acid did not increase the absorption of caffeine. The intestinal transfer of caffeine alone was studied at low concentrations (where caffeine exists mainly in monomeric form) and at high concentrations (where significant self-association occurs). The intestinal transfer rate constant of caffeine at high concentrations was significantly lower than at low concentrations. The mechanism of this effect was explored.