The fate of chronically consumed caffeine in the monkey (Macaca fascicularis)

The metabolic fate of chronically administered caffeine was examined in monkeys. Caffeine and equal parts of citric acid were added to the drinking water of four female monkeys (Macaca fascicularis). The concentration was gradually increased over a 10-week period to 0.35 mg/ml for three of the monkeys. A monkey that was lactating, but had no infant, was exposed to caffeine in the drinking water at a concentration of 0.30 mg/ml. At these doses, administered for up to 50 weeks, there were no overt signs of toxicity as indicated by food and fluid consumption, body weight, or general condition of the monkey. Mean plasma caffeine concentrations were 3.8, 5.7, and 5.9 micrograms/ml, while mean plasma theophylline concentrations were 11.8, 13.0, and 20.1 micrograms/ml, respectively for the monkeys receiving 0.35 mg/ml. Mean plasma caffeine and theophylline concentrations for the lactating monkey were 10.7 and 21.4 micrograms/ml, while mean milk concentrations were 10.5 and 17.6 micrograms/ml, respectively, indicating that caffeine and its major metabolite theophylline are readily excreted in milk. The high plasma theophylline levels indicate that caffeine metabolism in the monkeys differs from that in humans. Theophylline was the main urinary metabolite. In addition, large amounts of 1.3-dimethyluric acid were excreted in the urine but only traces of this metabolite were found in the plasma. After withdrawal of caffeine, plasma caffeine levels decreased to almost zero in the first 24 hr with a half-life of 5.5 hr, and plasma theophylline levels declined with a half-life of 12.7 hr.