title: Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits.
abstract: OBJECTIVE
  Paracetamol is one of the most common analgesics and antipyretics applied in health care. The aim of the study was to investigate the influence of the time-of-day administration on the paracetamol pharmacokinetics and its penetration into aqueous humour (AH).
  
  
  METHODS
  Rabbits were divided into three groups: I-receiving paracetamol at 08.00 h, II-receiving paracetamol at 16.00 h, and III-receiving paracetamol at 24.00 h. Paracetamol was administered intravenously at a single dose of 35 mg/kg. The concentrations of paracetamol and its metabolite (paracetamol glucuronide) in the plasma, as well as in AH were measured with the validated HPLC-UV method.
  
  
  RESULTS
  No significant differences in the pharmacokinetic parameters of paracetamol was observed. When the drug was administered at 24.00 h,  elimination half-life (t1/2kel) of paracetamol glucuronide was longer than when the drug was administered 08.00 h (P = 0.0193). In addition, a statistically significant increase in the paracetamol glucuronide/paracetamol ratio was observed when the drug was administered at 08.00 vs. 16.00 h (P ≤ 0.0001) and 24.00 h (P ≤ 0.0001).
  
  
  CONCLUSIONS
  There was no chronobiological effect on the pharmacokinetic parameters of paracetamol.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karbownik
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
authors.affiliation: Department of Teaching Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland. plotekw@poczta.onet.pl.
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Płotek
authors.affiliation: Polpharma Biologics, ul. Trzy Lipy 3, 80-172, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Pharmaceutical Technology, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cerbin-Koczorowska
authors.affiliation: Department of Animal Science, Iowa State University, 239E Kildee Hall, Ames, IA, 50011, USA.|Hy-Line International, 2583 240th Street, Dallas Center, IA, 50063, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolc
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061605:Administration, Intravenous / Q000379:methods; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D006207:Half-Life; D011817:Rabbits
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen