Caffeine is suspected to initiate the abuse of caffeine-containing analgesics. To clarify this matter the study investigated the effects of aspirin alone and in combination with caffeine on mood and cardiovascular parameters before, during, and after pain induction through mechanical stimulation. 96 healthy middle-aged women--all habitual coffee drinkers--were randomly designed to receive 0 or 500 mg aspirin together with 0, 50, or 100 mg caffeine administered in a double-blind design. Aspirin did not change ratings of mood scales. Caffeine decreased scores on negative mood scales, especially on the anxiety/sadness scale. The combination of aspirin and caffeine failed to increase any score on scales measuring positive moods. Only a few interactions are noticed. The results do not support the suggestion that caffeine increases the potential for abuse of aspirin

Caffeine is an effective analgesic adjuvant because it increases the antinociceptive effect of NSAIDs while reducing the probability of side effects. The mechanism by which caffeine increases the antinociceptive action of NSAIDs does not appear to include a pharmacokinetic interaction. The potentiation appears to be due to a pharmacokinetic mechanism including actions at the central and the peripheral levels. Because caffeine shifts the effect-compartment concentration-effect relation of NSAIDs to the left and this relationship is sigmoidal, there is no potentiation if the NSAID concentrations are too high or too low with respect to EC(50). The best potentiation can be observed if the NSAID doses used yield effect-compartment concentrations in the vicinity of EC(50). Therefore further investigation of the PK/PD relations of caffeine-NSAID combinations for different pain states and intensities is needed to optimize the therapeutic use of these mixtures

A study was undertaken, in 12 human volunteers, on the bioavailability of aspirin and the influence of simultaneous administration of caffeine thereon. Serial levels of salicylates were determined in plasma and urine. The results showed that administration of caffeine along with aspirin enhances the rate of absorption as well as concentration of aspirin in plasma. The urinary levels were parallel to the plasma levels, shoving increased levels of urinary salicylates under influence of caffeine.

Caffeine from dietary sources (mainly coffee, tea and soft drinks) is the most frequently and widely consumed CNS stimulant in the world today. Because of its enormous popularity, the consumption of caffeine is generally thought to be safe and long term caffeine intake may be disregarded as a medical problem. However, it is clear that this compound has many of the features usually associated with a drug of abuse. Furthermore, physicians should be aware of the possible contribution of dietary caffeine to the presenting signs and symptoms of patients. The toxic effects of caffeine are extensions of their pharmacological effects. The most serious caffeine-related CNS effects include seizures and delirium. Other symptoms affecting the cardiovascular system range from moderate increases in heart rate to more severe cardiac arrhythmia. Although tolerance develops to many of the pharmacological effects of caffeine, tolerance may be overwhelmed by the nonlinear accumulation of caffeine when its metabolism becomes saturated. This might occur with high levels of consumption or as the result of a pharmacokinetic interaction between caffeine and over-the-counter or prescription medications. The polycyclic aromatic hydrocarbon-inducible cytochrome P450 (CYP) 1A2 participates in the metabolism of caffeine as well as of a number of clinically important drugs. A number of drugs, including certain selective serotonin reuptake inhibitors (particularly fluvoxamine), antiarrhythmics (mexiletine), antipsychotics (clozapine), psoralens, idrocilamide and phenylpropanolamine, bronchodilators (furafylline and theophylline) and quinolones (enoxacin), have been reported to be potent inhibitors of this isoenzyme. This has important clinical implications, since drugs that are metabolised by, or bind to, the same CYP enzyme have a high potential for pharmacokinetic interactions due to inhibition of drug metabolism. Thus, pharmacokinetic interactions at the CYP1A2 enzyme level may cause toxic effects during concomitant administration of caffeine and certain drugs used for cardiovascular, CNS (an excessive dietary intake of caffeine has also been observed in psychiatric patients), gastrointestinal, infectious, respiratory and skin disorders. Unless a lack of interaction has already been demonstrated for the potentially interacting drug, dietary caffeine intake should be considered when planning, or assessing response to, drug therapy. Some of the reported interactions of caffeine, irrespective of clinical relevance, might inadvertently cause athletes to exceed the urinary caffeine concentration limit set by sports authorities at 12 mg/L. Finally, caffeine is a useful and reliable probe drug for the assessment of CYP1A2 activity, which is of considerable interest for metabolic studies in human populations

OBJECTIVE: To assess whether codeine and caffeine enhance the analgesic effect of aspirin in post-operative pain. METHOD: Systematic overview of the literature and meta-analysis of published randomized controlled trials (RCTs). RESULTS: Codeine 60 mg leads to a small increase in the analgesic effect of 650 mg of aspirin when total pain relief score (TOTPAR%) is used as a efficacy end-point. This increased effect was not seen when sum of pain intensity (SPID%) and proportions of patients responding with moderate to excellent pain relief were used as outcome measures. Caffeine did not enhance the analgesic effect of aspirin. CONCLUSION: Codeine 60 mg may produce a small increase in the analgesic effect of aspirin 650 mg. However, this effect is not clinically meaningful. Caffeine has no adjuvant analgesic effect. At over-the-counter (OTC) doses, caffeine and codeine are not useful in aspirin formulations

The objective of this study was to determine the influence of caffeine on aspirin bioavailability and pharmacokinetics in man. Two lots of the drugs were compared. The first lot (Lot # 1), which was caffeine-free, contained 650 mg aspirin plus 60 mg citric acid, whereas the second lot (Lot # 2) was caffeine-aspirin combination (650 mg aspirin plus 120 mg caffeine citrate, equivalent to 60 mg anhydrous caffeine). On two different occasions (2 weeks apart), the subjects received these two lots of drugs orally, i.e., each volunteer was given 650 mg aspirin (Lot # 1) or 650 mg aspirin plus 120 mg caffeine citrate (Lot # 2). It was found that caffeine significantly increased the rate of appearance as well as the maximum concentration of the salicylate in plasma by about 31 and 15 per cent, respectively. The area under the plasma concentration-time curve (AUC0 affinity) of salicylate was statistically higher in the subjects given the drug combination as compared to those given aspirin alone. Other pharmacokinetic parameters of the salicylate remained unchanged. It was therefore concluded that caffeine can increase the bioavailability of aspirin in man without any other effects on the salicylate disposition.

The effects of caffeine on the pharmacokinetics and bioavailability of aspirin were studied in 12 healthy adult male volunteers. The subjects received 650 mg of aspirin or 650 mg of aspirin with 120 mg of caffeine citrate orally. It was found that caffeine significantly increased the rate of appearance as well as the maximum concentration of salicylate in the plasma by about 25% and 17%, respectively. Moreover, area under the plasma concentration-time curve of salicylate was significantly higher in the subjects given the drug combination as compared to those given aspirin alone. There was no change in the plasma half-life, volume of distribution and clearance of salicylate.