title: Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers.
abstract: BACKGROUND
  Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH.
  
  
  METHODS
  Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration.
  
  
  RESULTS
  After the first oral dose, initial plasma METH detection was within 0.25-2 h; c(max) was 14.5-33.8 micro g/L (10 mg) and 26.2-44.3 micro g/L (20 mg) within 2-12 h. In oral fluid, METH was detected as early as 0.08-2 h; c(max) was 24.7-312.2 micro g/L (10 mg) and 75.3-321.7 micro g/L (20 mg) and occurred at 2-12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21% +/- 25% and 24% +/- 11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was >2.5 micro g/L for up to 24 h in 9 of 12 individuals (mean, 7.3 +/- 5.5 micro g/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8 +/- 18.0 micro g/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36-72 h (mean, 58.3 +/- 14.5 h).
  
  
  CONCLUSIONS
  Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Dr., Baltimore, MD 21224, USA. rscheper@intra.nida.nih.gov
authors.forename: Raf J F
authors.initials: RJ
authors.lastname: Schepers
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Oyler
authors.forename: Robert E
authors.initials: RE
authors.lastname: Joseph
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Cone
authors.forename: Eric T
authors.initials: ET
authors.lastname: Moolchan
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000661:Amphetamine / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008694:Methamphetamine / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D009055:Mouth / Q000378:metabolism*; D013048:Specimen Handling / Q000379:methods
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000661:Amphetamine