The objective of this paper is to present a population PK model which adequately describes the time-concentration profiles of different doses of ctanercept (Enbrel) administered subcutaneously to subjects with moderate-to-severe psoriasis and to simulate the time courses of concentrations following 50 mg once weekly (QW) dosing. Pharmacokinetic (PK) data from three clinical studies with doses 25 mg QW 25 mg twice weekly (BIW) and 50 mg BIW, were used. A one-compartment model with gender, weight and time covariates on the apparent clearance and weight covariate on the apparent volume of distribution was developed. The population mean of the apparent steady state clearance in males was 0.129 l/h. compared to 0.148 l/h in females. The clearance varied with time being lower in the first 2 weeks of the therapy, increasing sharply during weeks 3-4. and converging gradually after that to its steady state level. The population mean of the apparent volume of distribution also varied with time and was 16.11 during week 1, 20.01 during weeks 2-4 and 22.51 after week 4. The population PK model adequately described the observed concentration-time profiles in subjects with psoriasis. Despite a somewhat different covariate set, the parameter estimates of the population PK model for etanercept are very similar between the psoriasis and rheumatoid arthritis populations. The population PK model was used to simulate the pharmacokinetic profiles after a novel 50 mg QW dosing regimen. The simulations show good agreement with the observed data from 84 subjects participating in a fourth study (50 mg QW dose) used as an external validation set. The simulations of the 50 mg QW and the 25 mg BIW dosing regimens show that there is a significant overlap between the profiles yielding similar steady state exposures with both dosing regimens. The latter is an indication that the respective efficacy and safety profiles after those two dosing regimens are likely to be similar.