Pharmacokinetic drug-drug interaction between erlotinib and paracetamol: A potential risk for clinical practice
Erlotinib is a tyrosine kinase inhibitor available for the treatment of non-small cell lung cancer. Paracetamol is an analgesic agent, commonly used in cancer patients. Because these drugs are often co-administered, there is an increasing issue of interaction between them.Objective:
The aim of the study was to investigate the effect of paracetamol on the pharmacokinetic parameters of erlotinib, as well as the influence of erlotinib on the pharmacokinetics of paracetamol.Methods:
The rabbits were divided into three groups: the rabbits receiving erlotinib (IER), the group receiving paracetamol (IIPR), and the rabbits receiving erlotinib + paracetamol (IIIER + PR). A single dose of erlotinib was administered orally (25 mg) and was administered intravenously (35 mg/kg). Plasma concentrations of erlotinib, its metabolite (OSI420), paracetamol and its metabolites – glucuronide and sulphate were measured with the validated method.Results:
During paracetamol co-administration we observed increased erlotinib maximum concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) by 87.7% and 31.1%, respectively. In turn, erlotinib lead to decreased paracetamol AUC0-∞ by 35.5% and Cmax by 18.9%. The mean values of paracetamol glucuronide/paracetamol ratios for Cmax were 32.2% higher, whereas paracetamol sulphate/paracetamol ratios for Cmax and AUC0-∞ were 37.1% and 57.1% lower in the IIPR group, when compared to the IIIER + PR group.Conclusions:
Paracetamol had significant effect on the enhanced plasma exposure of erlotinib. Additionally, erlotinib contributed to the lower concentrations of paracetamol. Decreased glucuronidation and increased sulphation of paracetamol after co-administration of erlotinib were also observed.