Plasma Caffeine Levels Research Articles

In vivo N(7) Méthylation of Theophylline to Caffeine in Premature Infants

We studied the metabolism of theophylline in premature neonates by the use of molecules labelled with stable isotopes. 2 prematures received from birth up to 8th day of life 3 mg/kg/8 h of a mixed solution containing 46% of labelled and 54% of unlabelled theophylline. Plasma levels of caffeine and theophylline, measured by gas chromatographic mass spectrometric analysis, demonstrated the in vivo biotransformation of theophylline to caffeine in prematures.

Plasma xanthine levels in low birthweight infants treated or not treated with theophylline.

The use of theophylline in the management of apnoea in the newborn was studied in 33 preterm infants. Infants received a dose of 3 mg/kg, 13 of them every six hours, the remaining 20 every eight hours. All the infants had significantly fewer apnoeic episodes. In a pharmacokinetic study, the half life of theophylline was 30.3 +/- 7.2 hours and the clearance rate was 23.9 +/- 5.06 ml/kg per hour (means and SD). The plasma theophylline level remained constant at between 13 and 15 mg/l from the 5th day of treatment but, at the same time, the plasma levels of caffeine rose to a mean level of 4.4 mg/l. Caffeine was detectable in plasma at birth, and in preterm infants not receiving theophylline; plasma levels of caffeine tended to be similar to the levels in their mothers' milk. These observations have led to clear conclusions on the optimum timing and dosage of theophylline, and on the need to monitor plasma levels of both theophylline and caffeine in newborn infants treated with theophylline.

Effects of Caffeine on Plasma Renin Activity, Catecholamines and Blood Pressure

Using a double-blind, randomized, cross-over protocol, we studied the effect of a single dose of oral caffeine on plasma renin activity, catecholamines and cardiovascular control in nine healthy, young, non-coffee drinkers maintained in sodium balance throughout the study period. Caffeine (250 mg) or placebo was administered in a methylxanthine-free beverage to overnight-fasted supine subjects who had had no coffee, tea or cola in the previous three weeks. Caffeine increased plasma renin activity by 57 per cent, plasma norepinephrine by 75 per cent and plasma epinephrine by 207 per cent. Urinary normetanephrine and metanephrine were increased 52 per cent and 100 per cent respectively. Mean blood pressure rose 14/10 mm Hg one hour after caffeine ingestion. There was a slight fall and then a rise in heart rate. Plasma caffeine levels were usually maximal one hour after ingestion but there was considerable individual variation. A 20 per cent increase in respiratory rate correlated well with plasma caffeine levels. Under the conditions of study caffeine was a potent stimulator of plasma renin activity and adrenomedullary secretion. Whether habitual ingestion has similar effects remains to be determined.

Effect of Caffeine on the Human Small Intestine

Methylxanthines produce intracellular accumulation of cyclic 3'5'-AMP (cAMP) by inhibition of phosphodiesterase and mucosal cAMP accumulation. Cyclic AMP is thought to mediate small intestinal secretion caused by some enterotoxins, hormones, and methylxanthines. These studies were designed to evaluate the effect of caffeine on small intestinal net fluid movement and transit times. The administration of caffeine in amounts ordinarily contained in many beverages and medications (75 to 300 mg) resulted in striking net secretion in the jejunum which lasted at least 15 minutes. This occurred in six of seven studies. Baseline net absorption of 0.5 ml per cm per hr was reversed to net secretion of 6.0 +/- 2.2 ml per cm per hr after oral caffeine ingestion (P less than 0.01). Net secretion also occurred in the ileum in seven of eight studies, but the onset of secretion appeared 35 min later than in the jejunum. These patterns of secretion correlated best with the passage of the intestinal bolus of caffeine rather than plasma caffeine levels. In contrast to other net secretory conditions, which increase the speed of transit, small intestinal transit times, as determined by dye dilution methods, were unchanged by caffeine. It is possible that methylxanthine-induced small intestinal secretion may play a role in the symptoms experienced by some patients with functional diarrhea.

Caffeine-stimulated acid and pepsin secretion: dose-response studies.

Gastric secretion of acid and pepsin in response to graded doses of intravenous caffeine and corresponding plasma caffeine levels were studied in 4 healthy human volunteers. The threshold for both acid and pepsin secretion was found with an infusion of 160 mg caffeine benzoate per hour. At a plasma caffeine level of about 20 mg/litre the maximal acid response was obtained which corresponded to 44% of the pentragastrin-stimulated maximal output. Four to five cups of coffee consumed over 4 to 5 hours produced a similar plasma caffeine level. A linear relationship was demonstrated between the plasma caffeine levels and the corresponding gastric acid and pepsin outputs. There was in addition a high correlation between the acid outputs and the corresponding pepsin outputs. It was concluded that both acid and pepsin secretion are stimulated by intravenous caffeine administration, but that acid output is stimulated to a greater degree than pepsin output.

BIOLOGICAL HALF-LIFE OF CAFFEINE IN PIGS

Five experiments were conducted with growing pigs to determine the biological half-life of caffeine after injection or various periods of ingestion. Peak plasma caffeine levels were reached within 5 hr after a single oral dose and 2 hr after intramuscular injection, and then declined with a biological half-life of about 12 hr. The caffeine content of tissues was approximately proportional to their water content and 6% of orally administered caffeine was excreted in the urine. Upon continuous ingestion of caffeine, peak plasma levels were reached within 2 days, indicating that accumulation was quite limited. When 1.5 g of caffeine per kg of feed was fed from weaning to market weight, the withdrawal of caffeine 2 days prior to slaughter was sufficient time to insure that caffeine levels in the liver, muscle, kidney and backfat were below 1 μg/g.

Central Mining--Rand Mines Group. Report for the year 1947

The use of theophylline in the management of apnoea in the newborn was studied in 33 preterm infants. Infants received a dose of 3 mg/kg, 13 of them every six hours, the remaining 20 every eight hours. All the infants had significantly fewer apnoeic episodes. In a pharmacokinetic study, the half life of theophylline was 30.3 +/- 7.2 hours and the clearance rate was 23.9 +/- 5.06 ml/kg per hour (means and SD). The plasma theophylline level remained constant at between 13 and 15 mg/l from the 5th day of treatment but, at the same time, the plasma levels of caffeine rose to a mean level of 4.4 mg/l. Caffeine was detectable in plasma at birth, and in preterm infants not receiving theophylline; plasma levels of caffeine tended to be similar to the levels in their mothers9 milk. These observations have led to clear conclusions on the optimum timing and dosage of theophylline, and on the need to monitor plasma levels of both theophylline and caffeine in newborn infants treated with theophylline.

Verhandlungen des ärztlichen Vereines in Hamburg

A 27 year-old deeply unconscious male patient with shallow spontaneous respiration was admitted to hospital following an epileptoid convulsion with a tentative diagnosis of cerebral trauma. On admission he was noted to have hyperpyrexia, tachycardia and hypertension. The clinical and laboratory findings pointed to intoxication. Aspiration of the stomach produced a large amount of coffee grounds, but not tablets or other poison. The plasma caffeine level was 29 micrograms/ml, which is potentially lethal. Therapy was commenced with a beta-blocker, an anticonvulsive drug and an antipyretic, and supportive symptomatic measures were undertaken. After 12 hours the patient was fully conscious, orientated and cooperative. He subsequently admitted having ingested about 500 g ground coffee with the intention of obtained a "high" state of drug intoxication, which he had successfully achieved on previous occasions with a smaller amount of coffee and without complications. The clinical picture was consistent with the expected signs of caffeine intoxication whereby the central effects of the substance remain to be clarified. This appears to be the first report of caffeine misused in this manner. In cases of intoxication with convulsions of uncertain aetiology, caffeine poisoning should be considered in the differential diagnosis.