PMID- 37378676
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231107
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 92
IP  - 3
DP  - 2023 Sep
TI  - Population pharmacokinetics and toxicity correlation analysis of free and 
      liposome-encapsulated doxorubicin in Chinese patients with advanced breast 
      cancer.
PG  - 181-192
LID - 10.1007/s00280-023-04559-y [doi]
AB  - PURPOSE: The objective of this study was to investigate the pharmacokinetic 
      characteristics of pegylated liposomal doxorubicin (PLD) in Chinese female 
      patients with advanced breast cancer by constructing population pharmacokinetic 
      (popPK) models of liposome-encapsulated and free doxorubicin. Additionally, the 
      relationship between pharmacokinetic parameters and drug-related adverse events 
      (AEs) was explored through toxicity correlation analysis. METHODS: A total of 20 
      patients with advanced breast cancer were selected from a PLD bioequivalence 
      study. All patients received a single intravenous dose of 50 mg/m(2) PLD. Plasma 
      concentrations were measured using liquid chromatography-tandem mass spectrometry 
      (LC-MS/MS). A popPK model was simultaneously built to characterize the 
      pharmacokinetic profiles of liposome-encapsulated and free doxorubicin by 
      non-linear mixed effects model (NONMEM). PLD-related toxicities were graded 
      according to the common terminology criteria for adverse events (CTCAE) v5.0. The 
      Spearman correlation analysis was conducted to explore the relationship between 
      pharmacokinetic parameters and drug-related AEs of both liposome-encapsulated 
      doxorubicin and free doxorubicin. RESULTS: The concentration-time profiles of 
      both liposome-encapsulated doxorubicin and free doxorubicin were well described 
      by a one-compartment model. The most common AEs to PLD were nausea, vomiting, 
      neutropenia, leukopenia, and stomatitis, most of which were grade I-II. The 
      toxicity correlation analysis results indicated that stomatitis was related to 
      the C(max) of liposome-encapsulated doxorubicin (P < 0.05). No other AEs were 
      found to be correlated with the pharmacokinetic parameters of either free or 
      liposome-encapsulated doxorubicin. CONCLUSION: A one-compartment model adequately 
      described the popPK characteristics of both liposome-encapsulated and free 
      doxorubicin in Chinese female patients with advanced breast cancer. Most AEs to 
      PLD were mild. Additionally, the occurrence of mucositis may be positively 
      correlated with the C(max) of liposome-encapsulated doxorubicin.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Xu, Gaoqi
AU  - Xu G
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Yang, Dihong
AU  - Yang D
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - He, Chaoneng
AU  - He C
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Zhong, Like
AU  - Zhong L
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Zhu, Junfeng
AU  - Zhu J
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Shu, Qi
AU  - Shu Q
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Ding, Haiying
AU  - Ding H
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Xin, Wenxiu
AU  - Xin W
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Tong, Yinghui
AU  - Tong Y
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China.
FAU - Zhu, Xiao
AU  - Zhu X
AD  - Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, 
      Fudan University, Shanghai, China. xiaozhu@fudan.edu.cn.
FAU - Fang, Luo
AU  - Fang L
AUID- ORCID: 0000-0003-1187-4195
AD  - Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy 
      of Sciences, Hangzhou, Zhejiang, China. fangluo@zjcc.org.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230628
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Liposomes)
RN  - 80168379AG (Doxorubicin)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 0 (Antibiotics, Antineoplastic)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/drug therapy
MH  - Liposomes
MH  - Chromatography, Liquid
MH  - East Asian People
MH  - Tandem Mass Spectrometry
MH  - Doxorubicin
MH  - *Neutropenia/chemically induced
MH  - *Stomatitis/chemically induced
MH  - Polyethylene Glycols
MH  - Antibiotics, Antineoplastic/adverse effects/pharmacokinetics
OTO - NOTNLM
OT  - Breast cancer
OT  - Mucositis
OT  - Pegylated liposomal doxorubicin
OT  - Population pharmacokinetics
OT  - Toxicity correlation analysis
EDAT- 2023/06/28 13:09
MHDA- 2023/10/23 00:45
CRDT- 2023/06/28 11:03
PHST- 2023/04/04 00:00 [received]
PHST- 2023/06/15 00:00 [accepted]
PHST- 2023/10/23 00:45 [medline]
PHST- 2023/06/28 13:09 [pubmed]
PHST- 2023/06/28 11:03 [entrez]
AID - 10.1007/s00280-023-04559-y [pii]
AID - 10.1007/s00280-023-04559-y [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2023 Sep;92(3):181-192. doi: 
      10.1007/s00280-023-04559-y. Epub 2023 Jun 28.