Individual patient AUC0�C168 h after day 1 and at steady state are shown in Figure 1. Serum trough concentrations of PEG-IFN ��-2a (40KD) appeared to reach steady state by week 8 for both dose groups (Figure 2), and plasma merely concentration�Ctime profiles following the first dose and at steady state are displayed in Figure 3. Table 2 Summary of single-dose and steady-state pharmacokinetic parameters for PEG-IFN ��-2a (40KD) 180 ��g or 270 ��g Figure 3 Mean serum plasma concentration�Ctime profiles of PEG-IFN ��-2a (40KD) from the two treatment groups (error bars = SD) at week 1 (a) and at week 12 (b) Figure 2 Mean serum trough concentrations of PEG-IFN ��-2a (40KD) from the two treatment groups (error bars = SD). 180 ��g/week (); 270 ��g/week () Figure 1 Individual patient AUC0�C168 after the first dose (week 1) and at steady state (week 12).

Open circles represent the individual AUC168 values. The mean values of each arm at week 1 and week 12 are plotted as solid horizontal lines and the median … The study results were compared with Roche data on file in non-obese patients (BMI < 30 kg m?2; range 18�C29; n= 105 observations) and obese patients (BMI �� 30 kg m?2; range 30�C51; n= 173 observations) with CHC. The mean steady-state serum Ctrough of PEG-IFN ��-2a (40KD) following 180 ��g dosing in the historical data sets for non-obese patients was 20.5 ng ml?1 (range 0.1�C59.2) and for obese patients 16.1 ng ml?1 (range 0.2�C52.4). In the present study in patients with BMI �� 30 kg m?2 mean steady-state serum Ctrough estimates for the 180 ��g week?1 dose was 11.

2 ng ml?1 (range 4.4�C18.5) and for the 270 ��g week?1 dose was 16.1 ng ml?1 (range 0.4�C44.2). Efficacy An SVR was recorded in 14 of 20 (70%) and 15 of 19 (79%) patients completing treatment with PEG-IFN ��-2a (40KD) 180 and 270 ��g week?1 plus ribavirin, respectively (Table 3). All nine patients with genotypes 2 and 3 achieved an SVR. Of the six patients who failed to achieve an SVR following PEG-IFN ��-2a (40KD) 180 ��g week?1 plus ribavirin, three were nonresponders and three relapsers. Four patients did not achieve an SVR following PEG-IFN ��-2a (40KD) 270 ��g week?1 plus ribavirin: one was a nonresponder and three relapsers. Table 3 Viral response from the two treatment groups Safety assessment All patients enrolled in the trial experienced at least one treatment-related adverse event, although most were mild in severity and no patients required premature withdrawal of medication due to an adverse event or laboratory abnormality.

Adverse events were typical of those experienced during treatment with pegylated interferons and ribavirin and there was no clear dose response in adverse events. The most notable differences in the rates of adverse events between the two groups (defined as a rate of more than three patients Batimastat in one group vs. the other) for PEG-IFN ��-2a (40KD) 180 ��g week?1 and PEG-IFN ��-2a (40KD) 270 ��g week?1 groups were dry skin (12 vs.