title: Comparison of plasma and saliva concentrations of levetiracetam following administration orally as a tablet and as a solution in healthy adult volunteers.
abstract: OBJECTIVE
  Concentrations in saliva, as an alternative to concentrations in blood, can be advantageous for the monitoring of antiepileptic agents. This study assesses the relationship between saliva and plasma concentrations of levetiracetam after administration orally as a solution and as a tablet. The possibility that saliva concentrations of the drug are altered by contamination in the buccal cavity was also examined.
  
  
  METHODS
  4 healthy male subjects received a single 750 mg oral dose of levetiracetam as a 10% solution and 4 subjects received three 250 mg tablets (750 mg). Levetiracetam concentrations in plasma and saliva were monitored for 24 hours post dose.
  
  
  RESULTS
  In subjects receiving the levetiracetam solution, maximum saliva concentrations were observed at the first collection point (15 min) after administration and these were 19-74 times higher than corresponding plasma levels. The mean saliva/plasma ratio rapidly decreased thereafter, becoming stable after 4 hours. In subjects receiving tablets, levetiracetam concentration profiles for saliva paralleled the plasma concentration profiles with a fairly constant saliva/plasma concentration ratio throughout the 24-hour sampling period. A significant linear correlation between levetiracetam saliva and plasma concentrations was demonstrated (Pearson r = 0.88; p < 0.001 for tablet (n = 35) and r = 0.87; p < 0.001 for solution at times > or = 4 hours post-dose (n = 20)). The saliva to plasma concentration ratio was 1.11 (95% confidence interval: 0.99 - 1.22) following tablet intake, and 1.55 (95% CI: 1.34 1.77) following oral solution (> or = 4 hours post dose).
  
  
  CONCLUSIONS
  Using saliva to monitor therapeutic exposure to levetiracetam is feasible beginning 15 minutes after tablet intake but beginning 4 hours after intake of an oral solution.
authors.affiliation: Stuivenberg Hospital, SGS Clinical Research Unit, Antwerp, Belgium.
authors.forename: R L
authors.initials: RL
authors.lastname: Lins
authors.forename: C
authors.initials: C
authors.lastname: Otoul
authors.forename: F
authors.initials: F
authors.lastname: De Smedt
authors.forename: R
authors.initials: R
authors.lastname: Coupez
authors.forename: A
authors.initials: A
authors.lastname: Stockis
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods; D005240:Feasibility Studies; D006801:Humans; D000077287:Levetiracetam; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D019999:Pharmaceutical Solutions; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D012016:Reference Values; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism*; D013607:Tablets; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D019999:Pharmaceutical Solutions; D013607:Tablets; D000077287:Levetiracetam; D010889:Piracetam