Pharmacokinetic changes and influencing factors of amphotericin B in patients with severe invasive fungal infection

Abstract

Abstract: Objective To investigate the PK characteristics and target value of deoxycholate amphotericin B in patients with severe invasive fungal infection and analyze the influencing factors of PK changes. Methods Patients with severe invasive fungal disease who were admitted to the Department of Critical Care Medicine of Zhongda Hospital Affiliated to Southeast University from November 2018 to November 2022 and received deoxycholate amphotericin B infusion therapy were selected. Amphotericin B was gradually accumulated from 1 mg/d to 50 mg/d, and was continuously pumped intravenously for 6 h. On the 7th and 14th day of administration, 2 mL of peripheral blood was collected every time before administration and at 1, 3,6,9 and 12 h after administration. The concentration of amphotericin B in plasma was determined by LC-MS/MS method. The PK characteristics of amphotericin B were observed and the influencing factors of PK changes were analyzed by linear regression method. Results A total of 12 patients with severe invasive fungal disease were included. Compared with the pharmacokinetic parameters of deoxycholate amphotericin B obtained in normal subjects, the trough concentration, CL, half-life (t_1/2), and AUC of amphotericin B in severe IFI patients were higher than those in healthy subjects (all P＜0.05 ), and its Cmax and Vd were higher. Univariate analysis showed that real-time APACHE II score may be the influencing factor of amphotericin B peak concentration (P=0.008). Conclusion The trough concentration, CL, half-life (t_1/2) and AUC of amphotericin B in patients with severe IFI were higher than those in healthy subjects, but there was no significant difference in Cmax between the two groups. Real-time APACHE II score might be the influencing factor of amphotericin B peak concentration. The faster cumulative acceleration of amphotericin B did not show a significant increase in the incidence of immediate adverse reactions, and there was a higher pharmacodynamic concentration.

Key words: amphotericin B, invasive fungal infection, pharmacokinetics, critical care patient

CLC Number:

R519
R978.5

WANG Haofei, WANG Jinlong, HU Wenhan, SONG Qianwen, WU Changde, HE Jie, HU Linlin, XU Jingyuan, LI Qing, PAN Chun, XIE Jianfeng, HUANG Yingzi. Pharmacokinetic changes and influencing factors of amphotericin B in patients with severe invasive fungal infection[J]. Chinese Journal of Mycology, 2023, 18(2): 117-122.

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