Caffeine-phenacetin interaction in the rat: effects on absorption, metabolism and locomotor activity

Abstract

The interactive effects of caffeine and phenacetin on the locomotor activity of the DA rat involved changes in absorption and metabolism as well as effects possibly exerted at the cns level. Phenacetin initially retarded the absorption of caffeine when coadministered by gavage but not when caffeine was given intraperitoneally and phenacetin orally. Phenacetin also increased the time for the plasma/caffeine concentration to peak, increased its peak concentration and prolonged its presence in the plasma. Urinary excretion patterns, suggested a blockade of the N‐demethylation of caffeine by phenacetin. In contrast, caffeine had only a minor influence on the absorption and metabolism of phenacetin. The locomotor effects of the caffeine‐phenacetin combination reflected the absorptive and metabolic interactions which occurred. Caffeine‐induced hyperactivity was initially masked by phenacetin in a dose‐dependent manner but after 2 h, when the plasma phenacetin concentrations were much lower, its retarding influence on caffeine metabolism became apparent and hyperactivity consequent upon an elevated plasma caffeine concentration was seen. Phenacetin also antagonized the hyperactive effects of theophylline and of (+)‐amphetamine.

Comparative study of the therapeutic effects of brands of paracetamol (acetaminophen) on experimentally induced dental pain

“…The combination of paracetamol and caffeine was proposed by Laska et al 5 . Caffeine is believed to be capable of potentiating the effect of an analgesic by increasing its absorption 4 hence Panadol-Extra® is expected to be a more potent analgesic than Panadol®.…”

“…the treatment of pain from everyday causes and for febrile infections with Cafffeine and other methylxanthines are believed to increase the absorption of acetylsalicylic acid in man. Similarly, simultaneous ingestion of phenacetin with caffeine not only delays the breakdown of caffeine but also potentates its effect 4 . Some bases for using caffeine in combination with analgesics may perhaps be found in the demonstrable efficacy of caffeine in migraine and headaches, an effect that may be due to its intrinsic power of raising vessel tone in the cranial area.…”