Details

Autor(en) / Beteiligte

• Li, Xian-ping
• Li, Jing
• Yan, Heng
• Hou, Sheng
• Qian, Wei-zhu
• Chen, Yong-chuan
• Tang, Min
• Li, Bo-hua
• Zhang, Da-peng
• Zhou, Bo
• Wang, Hao
• Hao, Fei
• Guo, Ya-jun

Titel

Pharmacokinetic and pharmacodynamic study of LFA3Ig fusion protein in healthy volunteers and patients with psoriasis

Ist Teil von

• Acta pharmacologica Sinica, 2008-09, Vol.29 (9), p.1077-1085

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Aim： 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 T1/2ke of 307.9±32.7 h. The steady state was attained after the fifth administration. Conclusion： 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.