Efalizumab is cleared by dose-dependent non-linear saturable elimination. Mean steady-state clearance is 24.3± 18.5 and 15.7± 12.6 ml/kg/day for the 1 mg/kg/ week and 2 mg/kg/week groups, respectively. The elimination half-lifewasabout6.21±3.11 daysfor the 1 mg/ kg/week group and 7.4 ± 2.5 days in the 2 mg/kg/week group. Tend at steady state is 25.5 ± 1.6 days at 1 mg/kg/ week and 44 ± 10 days at 2 mg/kg/week.
Efalizumab shows dose-dependent non-linear phar-macokinetics, which can be explained by its saturable specific binding to cell surface receptors CD11a. Clearance was more rapid at lower doses, suggesting a receptor-mediated mechanism at drug levels below 10 ^g/ml.
In a population pharmacokinetic analysis of 1,088 patients, body weight was found to be the most significant covariate affecting efalizumab clearance. Other covariates such as baseline Psoriasis Area and Severity Index (PASI), baseline lymphocyte count and age had modest effects on clearance; gender and ethnic origin had no effect.
Additional pharmacokinetic data are available from an open-label extended treatment trial in which patients who responded to an initial treatment of efalizumab, 2 mg/kg, for 12 weeks, received the drug in a maintenance phase for up to 33 months at a dose of 1 mg/kg. Pharmacokinetic analysis of each 12-week treatment period for up to 15 months showed that steady-state trough levels remained constant during continuous efalizumab dosing. There was no evidence of efalizumab accumulation or alteration of the phar-macokinetic profile of efalizumab during long-term continuous dosing.
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