title: Circadian rhythmicity in levodopa pharmacokinetics in patients with Parkinson disease.
abstract: OBJECTIVE
  The purpose of this study was to compare daytime and nighttime plasma pharmacokinetics (PK) of levodopa in patients with Parkinson disease.
  
  
  METHODS
  Four-hour plasma profiles of levodopa were captured in 8 patients with Parkinson disease after the second daily levodopa dose and after the identical dose at bedtime. Patients were fasting 2 hours before and 2 hours after dose intakes, except standardized amounts of tap water. Body position was upright during daytime testing and supine during nighttime testing. Four patients were additionally tested at daytime in supine position.
  
  
  RESULTS
  The absorption rate was significantly delayed at nighttime dosing. The time at which the maximum peaks occurred was delayed from 25 (15-240) to 105 (20-240) minutes, respectively. Maximum concentrations were significantly lower at night, but the plasma exposure (area under the curve, 0-4 hours) was unaffected. Supine daytime plasma PK was in between day and night results.
  
  
  CONCLUSIONS
  There is a slower absorption rate of levodopa during nighttime, probably related to delayed gastric emptying. However, the extent of absorption and bioavailability were unaffected. As the effect of posture on plasma PK was less than the effect of nighttime, this study suggests that the circadian rhythm has a pronounced effect on gastric emptying and absorption rate. Nevertheless, body position may also be an important factor, and it can be recommended that levodopa tablets be taken in upright position that probably should be sustained for at least 30 minutes.
authors.affiliation: Department of Neuroscience, Neurology, and daggerDepartment of Pharmacy, BMC, Uppsala University, Uppsala, Sweden. dag.nyholm@neuro.uu.se
authors.forename: Dag
authors.initials: D
authors.lastname: Nyholm
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.forename: Matias
authors.initials: M
authors.lastname: Estrada
authors.forename: Sten-Magnus
authors.initials: SM
authors.lastname: Aquilonius
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002940:Circadian Rhythm / Q000187:drug effects*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa