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. 2018 Oct;36(5):819-827.
doi: 10.1007/s10637-018-0573-1. Epub 2018 Feb 20.

The Concomitant Use of Lapatinib and Paracetamol - The Risk of Interaction

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Free PMC article

The Concomitant Use of Lapatinib and Paracetamol - The Risk of Interaction

Agnieszka Karbownik et al. Invest New Drugs. .
Free PMC article

Abstract

Lapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer patients are polymedicated, which involves high risk of drug interactions during therapy. The aim of the study was to assess the interaction between lapatinib and paracetamol in rats. The rats were divided into three groups of eight animals in each. One group received lapatinib + paracetamol (IL + PA), another group received lapatinib (IIL), whereas the last group received paracetamol (IIIPA). A single dose of lapatinib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. Plasma concentrations of lapatinib, paracetamol and its metabolites - glucuronide and sulphate, were measured with the validated HPLC-MS/MS method and HPLC-UV method, respectively. The pharmacokinetic parameters of both drugs were calculated using non-compartmental methods. The co-administration of lapatinib and paracetamol increased the area under the plasma concentration-time curve (AUC) and the maximum concentration (Cmax) of lapatinib by 239.6% (p = 0.0030) and 184% (p = 0.0011), respectively. Lapatinib decreased the paracetamol AUC0-∞ by 48.8% and Cmax by 55.7%. In the IL + PA group the Cmax of paracetamol glucuronide was reduced, whereas the Cmax of paracetamol sulphate was higher than in the IIIPA group. Paracetamol significantly affected the enhanced plasma exposure of lapatinib. Additionally, lapatinib reduced the concentrations of paracetamol. The co-administration of lapatinib decreased the paracetamol glucuronidation but increased the sulphation. The findings of this study may be of clinical relevance to patients requiring analgesic therapy.

Keywords: Drug-drug interaction; Lapatinib; Paracetamol; Paracetamol glucuronide and paracetamol sulphate pharmacokinetics.

Conflict of interest statement

Conflict of interest

Author AK declares no conflict of interest. Author ES declares no conflict of interest. Author KS declares no conflict of interest. Author TG declares no conflict of interest. Author AK declares no conflict of interest. Author SP declares no conflict of interest. Author AW declares no conflict of interest. Author MM declares no conflict of interest. Author JP declares no conflict of interest. Author ZJK declares no conflict of interest. Author EG declares no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines concerning the care and use of animals were followed.

Figures

Fig. 1
Fig. 1
Lapatinib (L) plasma concentration–time profiles in rats receiving lapatinib + paracetamol (IL + PA) and lapatinib (IIL)
Fig. 2
Fig. 2
Paracetamol (PA) plasma concentration–time profiles in rats receiving paracetamol (IIIPA) and lapatinib + paracetamol (IL + PA)
Fig. 3
Fig. 3
Paracetamol glucuronide (PA-G) concentration–time profiles in rats receiving paracetamol (IIIPA) and lapatinib + paracetamol (IL + PA)
Fig. 4
Fig. 4
Paracetamol sulphate (PA-S) concentration–time profiles in rats receiving paracetamol (IIIPA) and lapatinib + paracetamol (IL + PA)

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