Pharmacokinetic interaction between warfarin and aspirin in rats

Abstract

Abstract: AIM: To explore the pharmacokinetic interaction between warfarin and aspirin in rats at non-steady-state and steady-state.METHODS: Three groups of six rats each were used according to a parallel study. Group I (warfarin) received daily repeated 0.2 mg/kg intragastric administration. Group II (aspirin) received daily repeated 10 mg/kg intragastric administration. Group III (warfarin plus aspirin) was administered as drug combination, namely daily oral dose of 0.2 mg/kg warfarin and 10 mg/kg aspirin. The rats received once daily repeated oral administration for 6 days. Plasma drug concentrations were obtained at scheduled time points on the first and the 6th day after dosing. The pharmacokinetic profiles and calculated parameters were analyzed and compared.RESULTS: The pharmacokinetics of warfarin and aspirin were best fitted to a two-compartment and one compartment model, respectively. At non-steady-state, the concentration-time course and related parameters of warfarin and aspirin was not changed by each other. At steady-state, the pharmacokinetic characteristics of warfarin were also not changed by aspirin. However, after multiple doses, Aspirin increased the peak plasma concentration and area under the curve of warfarin at steady-state.CONCLUSION: At steady-state after multiple dosing, aspirin increased the exposure of warfarin, which indicates that the combination therapy may increase the bleeding risk. This increase may represent a safety concern. The results suggest some differences of pharmacokinetic properties between warfarin and aspirin combinations at steady state, which indicates that when warfarin and aspirin are administered together, therapeutic drug monitoring should be enhanced.

Key words: Warfarin, Aspirin, Drug interaction, Pharmacokinetics

CLC Number:

R969

HUANG Xiao-hui, WANG Xia-qin, TANG Hai-qin, WANG Qin, CHEN Yun, LI Jing, LI Jun. Pharmacokinetic interaction between warfarin and aspirin in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 189-194.

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