title: Pharmacokinetics of caffeine in plasma and saliva, and the influence of caffeine abstinence on CYP1A2 metrics.
abstract: OBJECTIVE
  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 100mg 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 24h. Caffeine and paraxanthine concentrations were measured using a validated HPLC assay.
  
  
  RESULTS
  There was a strong correlation between the paraxanthine/caffeine AUC(0-24) ratio (reference metric) and the paraxanthine/caffeine concentration (C(t) ) ratio at 4h (C(4) ) in both saliva and plasma (r≥0.75). The paraxanthine/caffeine AUC(0-24) 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 C(t) that correlated with the plasma paraxanthine/caffeine AUC(0-24) ratio in the 24-h abstinence period was 2 and 4h (r=0.88) in plasma, and 4 and 6h in saliva (r=0.70), while it was the saliva 4h time-point in the no abstinence period (r=0.78).
  
  
  CONCLUSIONS
  The saliva paraxanthine/caffeine concentration ratio at 4h was a suitable metric to assess CYP1A2 activity after oral administration of caffeine without the need for 24-h caffeine abstinence.
authors.affiliation: Faculty of Pharmacy, The University of Sydney, NSW, Australia.
authors.forename: Vidya
authors.initials: V
authors.lastname: Perera
authors.forename: Annette S
authors.initials: AS
authors.lastname: Gross
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McLachlan
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004796:Clinical Enzyme Tests / Q000379:methods*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008657:Metabolic Clearance Rate; D012016:Reference Values; D012463:Saliva / Q000378:metabolism*; D013806:Theophylline / Q000378:metabolism; D055815:Young Adult
chemical_list: D002110:Caffeine; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine