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

Abstract

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). Rabbits were divided into three groups: I-receiving paracetamol at 08.00h, II-receiving paracetamol at 16.00h, and III-receiving paracetamol at 24.00h. Paracetamol was administered intravenously at a single dose of 35mg/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. No significant differences in the pharmacokinetic parameters of paracetamol was observed. When the drug was administered at 24.00h, elimination half-life (t 1/2kel) of paracetamol glucuronide was longer than when the drug was administered 08.00h (P=0.0193). In addition, a statistically significant increase in the paracetamol glucuronide/paracetamol ratiowas observed when the drug was administered at 08.00 vs. 16.00h (P≤0.0001) and 24.00h (P≤0.0001). There was no chronobiological effect on the pharmacokinetic parameters of paracetamol.