Agnieszka Karbownik1, Agnieszka Bienert1, Włodzimierz Płotek2, Tomasz Grabowski3, Magdalena Cerbin-Koczorowska4, Anna Wolc5,6, Edmund Grześkowiak1. 1. Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland. 2. 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. 3. Polpharma Biologics, ul. Trzy Lipy 3, 80-172, Gdańsk, Poland. 4. Department of Pharmaceutical Technology, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland. 5. Department of Animal Science, Iowa State University, 239E Kildee Hall, Ames, IA, 50011, USA. 6. Hy-Line International, 2583 240th Street, Dallas Center, IA, 50063, USA.
Abstract
BACKGROUND AND OBJECTIVES: 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 (t 1/2kel) 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.
BACKGROUND AND OBJECTIVES: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 (t 1/2kel) 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: P L Moller; S Sindet-Pedersen; C T Petersen; G I Juhl; A Dillenschneider; L A Skoglund Journal: Br J Anaesth Date: 2005-03-24 Impact factor: 9.166
Authors: Abdul E Mutlib; Theunis C Goosen; Jonathan N Bauman; J Andrew Williams; Shaila Kulkarni; Seva Kostrubsky Journal: Chem Res Toxicol Date: 2006-05 Impact factor: 3.739