Pharmacokinetics of the metabolites of abivertinib in Chinese patients with advanced NSCLC in a single and multiple dose group

doi:10.12092/j.issn.1009-2501.2018.10.010

Abstract

Abstract:

AIM: To evaluate the pharmacokinetics of the metabolites of abivertinib in Chinese patients with advanced nonsmall-cell lung cancer (NSCLC) after single and multiple dose of abivertinib maleate capsules. METHODS: Seven Chinese patients with advanced NSCLC were administered a single oral dose of 350 mg of abivertinib maleate capsule. After a washout period, three of them were administered 350 mg of abivertinib QD for 28 days, four were administered 175 mg of abivertinib twice a day for 28 days. The plasma concentrations of five metabolites of abivertinib were assayed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated with WinNonlin ver. 6.4. RESULTS: Among these five metabolites, the exposure of MII-2, a cysteine conjugate, was the highest, which was 3.32%-5.57% of the exposure of the parent drug. The exposures of M1 (N-demethylation) and M2 (N-oxidation) were 2.14%-4.24% and 0.56%-1.00% of the exposure of the parent drug, respectively. The exposures of M4 (N-dealkylation) and MII-1 (acetylcysteine conjugate) were low, most of the concentrations of MII-1 were blow the lower limit of quantitation (0.1 ng/mL). CONCLUSION: The exposures of the five metabolites monitored were no more than 10% of the exposure of the parent drug.

Key words: abivertinib, metabolite, pharmacokinetics, EGFR-TKI, liquid chromatography-tandem mass spectrometry

CLC Number:

WANG Lu, ZHENG Xin, WANG Weicong, ZHAO Hongyun, MA Yuxiang, ZHANG Li, HU Pei, JIANG Ji. Pharmacokinetics of the metabolites of abivertinib in Chinese patients with advanced NSCLC in a single and multiple dose group[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(10): 1147-1152.

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