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Protein unbound pharmacokinetics of ambroxol in the blood and brains of rats and the interaction of ambroxol with Polygala tenuifolia by multiple microdialysis

Authors Yang, Chao-Nan; Peng, Wen-Ya; Lin, Lie-Chwen; Tsai, Tung-Hu

Journal JOURNAL OF ETHNOPHARMACOLOGY , APR 6 2021,:269

DOI 10.1016/j.jep.2020.113764 PubMed 33383115

Abstract Ethnopharmacological relevance: Ambroxol elevates glucocerebrosidase (GCase) activity and reduces nigrostriatal alpha-synuclein burden to better ameliorate motor function in Parkinson''s disease (PD). Polygala tenuifolia is a potential alternative botanical medicine for the treatment of many nonmotor symptoms of PD commonly used in Taiwanese patients. Co-administration of these two medicines pose potential herb-drug interaction.Aim of the study: Our hypothesis is that ambroxol and P. tenuifolia may potentially possess herbal drug synergetic effects in the blood and brain.Materials and methods: To investigate this hypothesis, a multiple microdialysis system coupled with validated ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for rat blood and brain samples. Experimental rats were divided into three groups: low-dose and high-dose ambroxol alone (10 mg/kg, i.v. and 30 mg/kg, i.v., respectively) and ambroxol (10 mg/kg, i.v.) pretreated with P. tenuifolia extract (1 g/kg, p.o. for 5 consecutive days).Results: Ambroxol easily penetrated into the brain and reached a maximum concentration in the striatum at approximately 60 min after low- and high-dose treatment. The area under the concentration curve (AUC) ratio increased proportionally at the doses of 10 and 30 mg/kg, which suggested a linear pharmacokinetic manner of ambroxol. The brain penetration of ambroxol was approximately 30-34%, which was defined as the ambroxol AUC blood-to-brain distribution ratio (AUC(brain)/AUC(blood)). The P. tenuifolia extract did not significantly alter the pharmacokinetics of ambroxol in the blood and brain of rats.Conclusion: The present study suggests that it is safety without pharmacokinetic interactions for this dosing regimen to use P. tenuifolia extract and ambroxol together.

Species covered 远志 Polygala tenuifolia