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Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits

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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.

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Author information

Correspondence to Włodzimierz Płotek.

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Conflict of interest

The authors Agnieszka Karbownik, Agnieszka Bienert, Włodzimierz Płotek, Tomasz Grabowski, Magdalena Cerbin-Koczorowska, Anna Wolc, Edmund Grześkowiak declare that they have no conflict of interests. The authors disclose no financial, consulting, and personal relationships with people or organizations that could be perceived by readers as biasing the authors’ work.

Funding

The financial support was provided by the Poznan University of Medical Sciences only.

Ethics

The welfare of animals used for was respected. Authors adhered to ethical guidelines provided by Portaluppi, who recommended ethical criteria for biological rhythm research on animals proposed in Chronobiology International (Chronobiol Int. 2010;27:1911–29). The experiment protocol was approved by the local Ethics Committee for Animal Research. All procedures were performed in accordance with the Polish regulations for the handlings and use of laboratory animals (Nr of consent: 01/2015). The appropriate written consent from the local Ethics Committee for Animal Research is available if requested. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Karbownik, A., Bienert, A., Płotek, W. et al. Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits. Eur J Drug Metab Pharmacokinet 42, 489–498 (2017). https://doi.org/10.1007/s13318-016-0365-y

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Keywords

  • Paracetamol
  • Sunitinib
  • Dexmedetomidine
  • Aqueous Humour
  • Pain Treatment