PMID- 38306390
OWN - NLM
STAT- MEDLINE
DCOM- 20240212
LR  - 20240212
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 19
IP  - 2
DP  - 2024
TI  - Pharmacokinetic and safety profiles of mesalazine enema in healthy Chinese 
      subjects: A single- and multiple-dose study.
PG  - e0296940
LID - 10.1371/journal.pone.0296940 [doi]
LID - e0296940
AB  - Mesalazine is a well-established treatment for ulcerative colitis by oral or 
      topical administration. However, the pharmacokinetic (PK) and safety profiles of 
      mesalazine administered by an enema has not been clarified in Chinese population. 
      We conducted an open-label study to assess the PK and safety profiles of 
      mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 
      g/100 mL) once daily for 7 consecutive days. Blood and urine samples were 
      collected for assay of mesalazine and N-acetyl mesalazine by liquid 
      chromatography-tandem mass spectrometry. The PK and safety data were summarized 
      using descriptive statistics. The mean (standard deviation) maximum plasma 
      concentration (Cmax), area under plasma drug concentration-time curve from time 0 
      to the last measurable plasma concentration time point (AUC0-t) and elimination 
      half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) 
      h.ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In 
      multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. 
      The cumulative urinary excretion rate of parent and major metabolite of 
      mesalazine was 27.77%. After the last doe administration, 2.21% of the 
      administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in 
      urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 
      subjects (36.4%), including oral ulcer, toothache, upper respiratory tract 
      infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and 
      recovered spontaneously without treatment, and were not considered as related to 
      mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy 
      Chinese subjects. These findings support further clinical trials in Chinese 
      patients. Trial registration: This trial was registered to Chinese Clinical Trial 
      Registry (ChiCTR) at https://www.chictr.org.cn (registration number: 
      ChiCTR2300073148).
CI  - Copyright: (c) 2024 Cao et al. This is an open access article distributed under the 
      terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Cao, Yuran
AU  - Cao Y
AD  - Clinical Trial Institute, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Wang, Jingjing
AU  - Wang J
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Tang, Xingyu
AU  - Tang X
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Tian, Yan
AU  - Tian Y
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Yu, Jicheng
AU  - Yu J
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Liang, Hong
AU  - Liang H
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Wu, Jufang
AU  - Wu J
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Chen, Yuancheng
AU  - Chen Y
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Cao, Guoying
AU  - Cao G
AUID- ORCID: 0009-0005-7076-4553
AD  - Clinical Trial Institute, Huashan Hospital, Fudan University, Shanghai, China.
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20240202
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 4Q81I59GXC (Mesalamine)
SB  - IM
MH  - Humans
MH  - Administration, Oral
MH  - Area Under Curve
MH  - China
MH  - Chromatography, Liquid
MH  - Dose-Response Relationship, Drug
MH  - Healthy Volunteers
MH  - *Mesalamine/adverse effects
MH  - *Tandem Mass Spectrometry/methods
PMC - PMC10836682
COIS- The authors have declared that no competing interests exist.
EDAT- 2024/02/02 18:42
MHDA- 2024/02/05 06:43
PMCR- 2024/02/02
CRDT- 2024/02/02 13:43
PHST- 2023/07/03 00:00 [received]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2024/02/05 06:43 [medline]
PHST- 2024/02/02 18:42 [pubmed]
PHST- 2024/02/02 13:43 [entrez]
PHST- 2024/02/02 00:00 [pmc-release]
AID - PONE-D-23-13509 [pii]
AID - 10.1371/journal.pone.0296940 [doi]
PST - epublish
SO  - PLoS One. 2024 Feb 2;19(2):e0296940. doi: 10.1371/journal.pone.0296940. 
      eCollection 2024.