PMID- 38044946
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231205
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Comparison of pharmacokinetics and safety between CE-fosphenytoin sodium, 
      fosphenytoin sodium, and phenytoin sodium after intravenous and intramuscular 
      administration in healthy volunteers.
PG  - 1204075
LID - 10.3389/fphar.2023.1204075 [doi]
LID - 1204075
AB  - Background: Captisol((R))-enabled-fosphenytoin sodium (CE-fosphenytoin sodium) 
      injection is a modified formulation of fosphenytoin sodium. Objective: We aim to 
      compare the intravenous and intramuscular bioavailability and safety between 
      CE-fosphenytoin sodium, fosphenytoin sodium (Cerebyx((R))), and phenytoin sodium 
      (intravenous injection only). Methods: In pivotal study 1, 54 subjects were 
      divided into three sequence groups that receive intravenous injection of 250 mg 
      of phenytoin sodium equivalent (PE), CE-fosphenytoin sodium (T), or fosphenytoin 
      sodium (R1) and 250 mg of phenytoin sodium (R2) in period 1. After a 14-day 
      washout period, 36 subjects were randomized to two treatment sequence groups 
      (T-R1 or R1-T, n = 18 per group) in period 2, in which the subjects who received 
      R2 in period 1 were removed, those who received T in period 1 used R1 (T-R1), 
      while those who previously received R1 used T (R1-T). In pivotal study 2, a 
      single intramuscular dose of T (400 mg PE) or R1 (400 mg PE) was administered 
      according to the individual sequential treatment assignment in each period. There 
      was a washout (14 days) period before receiving the next period study drug. 
      Results: T and R1 have similar pharmacokinetic characteristics regarding total 
      and free phenytoin, showing bioequivalence of both drugs in the intravenous and 
      intramuscular administration. The geometric mean ratio was close to 1 
      (0.98-1.06). The AUC of total and free phenytoin in subjects who intravenously 
      received T and R1 was very similar to those who received R2, although their 
      C(max) was lower than that of the subjects who received R2. Overall, treatment 
      with T and R1 was safe and well-tolerated, without serious adverse events (SAEs) 
      or grade III adverse events (AEs). With intravenous (i.v.) or intramuscular 
      (i.m.) treatment, the incidence of drug-related AEs using T was similar to that 
      using R1. Treatment with T and R1 had clearly superior tolerability than that 
      with R2. Conclusion: CE-fosphenytoin sodium is a promising substitute for 
      fosphenytoin sodium. Clinical Trial Registration: 
      http://www.chinadrugtrials.org.cn/, CTR20202154 (11 November 2020).
CI  - Copyright (c) 2023 Li, Wu, Sun, Jin, Han, Xu, Liu, Zhang, Wang, Wang, Zhang, Zhang, 
      Liu and Ding.
FAU - Li, Xiaojiao
AU  - Li X
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Wu, Min
AU  - Wu M
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Sun, Jixuan
AU  - Sun J
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Jin, Weili
AU  - Jin W
AD  - Xi'an Xintong Pharmaceutical Research Co., Ltd., Xi'an, China.
FAU - Han, Lei
AU  - Han L
AD  - Xi'an Xintong Pharmaceutical Research Co., Ltd., Xi'an, China.
FAU - Xu, Jia
AU  - Xu J
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Liu, Jingrui
AU  - Liu J
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Wang, Jing
AU  - Wang J
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Wang, Daidi
AU  - Wang D
AD  - Xi'an Xintong Pharmaceutical Research Co., Ltd., Xi'an, China.
FAU - Zhang, Hanyi
AU  - Zhang H
AD  - Xi'an Xintong Pharmaceutical Research Co., Ltd., Xi'an, China.
FAU - Zhang, Qing
AU  - Zhang Q
AD  - Xi'an Xintong Pharmaceutical Research Co., Ltd., Xi'an, China.
FAU - Liu, Nini
AU  - Liu N
AD  - Xi'an Xintong Pharmaceutical Research Co., Ltd., Xi'an, China.
FAU - Ding, Yanhua
AU  - Ding Y
AD  - Phase I Clinical Trial Center, The First Hospital of Jilin University, Changchun, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20231117
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10691362
OTO - NOTNLM
OT  - CE-fosphenytoin sodium
OT  - fosphenytoin sodium
OT  - healthy volunteers
OT  - pharmacokinetics
OT  - safety
COIS- Authors WJ, LH, DW, HZ, QZ, and NL are employed by Xi'an Xintong Pharmaceutical 
      Research Co., Ltd. The remaining authors declare that the research was conducted 
      in the absence of any commercial or financial relationships that could be 
      construed as a potential conflict of interest.
EDAT- 2023/12/04 06:42
MHDA- 2023/12/04 06:43
PMCR- 2023/11/17
CRDT- 2023/12/04 04:25
PHST- 2023/04/12 00:00 [received]
PHST- 2023/10/31 00:00 [accepted]
PHST- 2023/12/04 06:43 [medline]
PHST- 2023/12/04 06:42 [pubmed]
PHST- 2023/12/04 04:25 [entrez]
PHST- 2023/11/17 00:00 [pmc-release]
AID - 1204075 [pii]
AID - 10.3389/fphar.2023.1204075 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Nov 17;14:1204075. doi: 10.3389/fphar.2023.1204075. 
      eCollection 2023.