Pharmacokinetics of caffeine in plasma and saliva, and the influence of caffeine abstinence on CYP1A2 metrics

Abstract Objectives To investigate the utility of metrics of CYP1A2 activity using caffeine as a probe, and saliva and plasma sampling with or without a 24-h caffeine abstinence. Methods This was a cross-over pharmacokinetic study in 30 healthy male subjects who received a single oral 100 mg caffeine dose after 24-h caffeine abstinence or after maintaining their regular caffeine intake (no caffeine abstinence). Serial blood and saliva samples were collected simultaneously over 24 h. Caffeine and paraxanthine concentrations were measured using a validated HPLC assay. Key findings There was a strong correlation between the paraxanthine/caffeine AUC0–24 ratio (reference metric) and the paraxanthine/caffeine concentration (Ct) ratio at 4 h (C4) in both saliva and plasma (r ≥ 0.75). The paraxanthine/caffeine AUC0–24 ratio in plasma and saliva did not differ between the 24-h caffeine abstinence and the no abstinence period (P > 0.05). The optimal paraxanthine/caffeine Ct that correlated with the plasma paraxanthine/caffeine AUC0–24 ratio in the 24-h abstinence period was 2 and 4 h (r = 0.88) in plasma, and 4 and 6 h in saliva (r = 0.70), while it was the saliva 4 h time-point in the no abstinence period (r = 0.78). Conclusions The saliva paraxanthine/caffeine concentration ratio at 4 h was a suitable metric to assess CYP1A2 activity after oral administration of caffeine without the need for 24-h caffeine abstinence.