Plasma and salivary pharmacokinetics of caffeine in man

Abstract

Plasma and salivary caffeine concentrations were measured by gas-liquid chromatography in 6 healthy caffeine-free volunteers following oral administration of 50, 300, 500 and 750 mg caffeine. Caffeine was also given to a single subject intravenously in doses of 300, 500 and 750 mg. Caffeine was rapidly absorbed and was completely available at all doses. The apparent first-order elimination rate constant decreased linearly with dose and was 0.163 +/- 0.081 h-1 for 50 mg and 0.098 +/- 0.027 h-1 for 750 mg. The total body clearance was unaffected by dose and was 0.98 +/- 0.38 ml/min/kg. There was a trend towards increasing apparent volume of distribution with increasing dose. A linear relationship existed between the area under the plasma concentration, time curve and dose and dose-normalised plasma concentration, time plots were superimposable. These findings suggest that caffeine obeys linear pharmacokinetics over the dose range investigated. Despite significant inter-individual differences in pharmacokinetic parameters there was good reproducibility within 5 subjects given 300 mg caffeine orally on 3 occasions. Salivary caffeine levels probably reflect the unbound plasma caffeine concentration and can be used to estimate the pharmacokinetic parameters of the drug. Overall the saliva/plasma concentration ratio was 0.74 +/- 0.08 but within subjects some time-dependence of the ratio was found with higher ratios initially (even after intravenous administration) and lower ratios at longer time intervals after the dose. Urinary elimination of caffeine was low and independent of dose: 1.83% of the dose was eliminated unchanged.

Multiscale modeling reveals inhibitory and stimulatory effects of caffeine on acetaminophen‐induced toxicity in humans

“…The relative contribution of phase I CYP isoforms vs. phase II enzymes in the PBPK models of APAP and CAF was 70:30, and 100:0, respectively ( Figure 2). The established reference PBPK models were validated for additional doses and individual subgroups by using clinical PK data from different studies not used for developing the reference PBPK models 11, 22, 23, 24, 26, 27. Note that all model parameters were left unchanged in this validation step except study parameters specifying the design of the clinical trials.…”

“…PD responses of CAF and APAP were therefore predicted for an in vivo situation by the application of PICD14 thereby coupling in vitro toxicity data with drug‐specific PBPK models. To validate the PBPK models, simulated drug concentrations of APAP, CAF, and their main metabolites (APAPC, acetaminophen cysteine; APAPG, acetaminophen glucuronide; APAPS, acetaminophen sulfate; PX, paraxanthine; TP, theophylline; and TB, theobromine) were first assessed with clinical PK profiles from several studies obtained for different dosage regimens 8, 11, 20, 21, 22, 23, 24, 25, 26, 27. Using an additive PD response model, the influence of CAF on APAP‐induced hepatotoxicity was analyzed for key cellular processes and individual genes.…”

The effect of caffeine on working memory load-related brain activation in middle-aged males

“…Saliva sampling is considered a good method for frequent measurement of caffeine pharmacokinetics (Newton et al, 1981;Suzuki et al, 1989), with a linear relationship reported between caffeine concentrations in saliva and plasma, and salivary caffeine levels reported to be around 80% of plasma levels (Perera et al, 2011;Zylber--Katz et al, 1984). Collection, storage and analysis procedures are supplied as Supplementary Material.…”

A Comparative Histopathological Effect of Caffeinated and Decaffeinated Coffee on the Histomorphology of the Kidney of Adult Male Albino Wistar Rats

“…Cortisol is a stress hormone that has a major role in facilitating the fight or flight mechanism. Under stress, cortisol provides the body with glucose by utilizing protein stores via gluconeogenesis in the liver [20]. Elevated cortisol level consistently produces glucose leading to increased blood sugar levels along with insulin suppression which causes the cells to be starved of glucose [21].…”