Pharmacokinetic And Pharmacodynamic Study Of LFA3Ig Fusion Protein In Healthy Volunteers And Patients With Psoriasis

Aim: To evaluate PK and PD of LFA3Ig fusion protein (rhLFA3IgFP) in healthy volunteers and patients with chronic plaque psoriasis. Methods: The clinical trials included two Phase I open study: Study 1 was an open-label dose escalation study in healthy volunteers, 24 healthy volunteers were randomized to receive rhLFA3IgFP intramuscularly; Study 2 was a single-group, open-label study in patients with chronic plaque psoriasis, 12 patients were administrated intramuscularly with rhLFA3IgFP at a dosage of 15 mg once a week for 8 wk. The serum concentrations of rhLFA3IgFP were measured by self-established enzyme-linked immunosorbent assay(ELISA). The concentration-time data were analyzed by compartmental analysis using the Practical Pharmacokinetic Program Version 97 (3p97: published by Chinese Pharmacological Association, Beijing, China). Results: In study 1, after intramuscular (i.m.)injection with rhLFA3IgFP at a dosage of 5, 15, and 25 mg, respectively, the concentration-time curves of rhLFA3IgFP were well fitted to a one-compartment open model, area under the plasma concentration-time curve (AUC: in study 1, AUC is from before administration to 1200 h after administration) increased linearly with dose. Apparent clearance rates (Cls/F) and elimination half-lives (T_1/2ke) had no significant differences among the groups. A transient, slight decline of CD4⁺ and CD8⁺ T-cell proportion was observed after administration; In study 2, after i.m. at a dosage of 15mg weekly for 8 wk, the concentration-time curves of rhLFA3IgFP fitted well to a one-compartment open model, with a T_1/2ke of 307.9±32.7 h. The steady state was attained after the fourth administration (d 28). Conclusion: Specificity, sensitivity, accuracy and precision of the self-established ELISA method can meet the requirements for PK and PD study. The PK behaviors of rhLFA3IgFP in healthy volunteers and patients with chronic plaque psoriasis complied with linear kinetics within the examined dose range. No conspicuous accumulation was observed after repeated administration at a dose level of 15 mg weekly for 8 wk. This trial provides valuable information for further phase II and phase III clinical trials.