Pharmacokinetic and pharmacodynamic study of LFA3Ig fusion protein in healthy volunteers and patients with psoriasis.
OBJECTIVE
To evaluate the pharmacokinetics (PK) and pharmacodynamics of the LFA3Ig fusion protein (LFA3IgFP) in healthy volunteers and patients with chronic plaque psoriasis.


METHODS
The clinical trials included 2 phase I open studies. Study 1 was an open-label dose escalation study in 24 healthy volunteers, and study 2 was a single-group, open-label study in 12 patients with chronic plaque psoriasis. The serum drug concentrations were measured, and the concentration-time data were analyzed by compartmental analysis using the Practical Pharmacokinetic Program.


RESULTS
In study 1, after intramuscular (im) administration at a dosage of 5, 15, and 25 mg, the concentration-time curves of LFA3IgFP fitted well to a 1 compartment open model. Areas under the concentration-time curves increased linearly with dose. Clearance rates (Cls/ F) and elimination half-lives (T1/2ke) had no significant difference between different dose groups. A transient, slight decline of CD(4+) and CD(8+) T-cell subsets was observed after administration. In study 2, after im administration at a dosage of 15 mg weekly for 8 weeks, the concentration-time curve was best fitted to a 1 compartment open model, with a T(1/2ke ) of 307.9+/-32.7 h. The steady state was attained after the fifth administration.


CONCLUSIONS
The PK behaviors of LFA3IgFP in healthy volunteers and patients with chronic plaque psoriasis complied with linear kinetics within the examined dose range. A significant accumulation was observed after repeated administration at a dose of 15 mg weekly for 8 weeks.
Li
Xian-ping
XP
International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, China.
Li
Jing
J
Yan
Heng
H
Hou
Sheng
S
Qian
Wei-zhu
WZ
Chen
Yong-chuan
YC
Tang
Min
M
Li
Bo-hua
BH
Zhang
Da-Peng
DP
Zhou
Bo
B
Wang
Hao
H
Hao
Fei
F
Guo
Ya-Jun
YJ
D000293:Adolescent; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000187:drug effects; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015203:Reproducibility of Results; D055815:Young Adult
C540586:LFA3-IgG1 fusion protein, human; D011993:Recombinant Fusion Proteins