Multiple-dose pharmacokinetics of peginterferon alfa-2b in patients with renal insufficiency.

Aim To evaluate the safety, tolerability and multiple-dose pharmacokinetics of pegylated interferon (PEG-IFN) alfa-2b in patients with moderate or severe renal insufficiency and in those with normal renal function. Methods In an open-label study, subjects with normal renal function ( creatinine clearance > 80 ml min(-1) per 1.73 m(2)) and patients with moderate (30-50 ml min(-1) per 1.73 m(2)) or severe (10-29 ml(-1) min(-1) per 1.73 m2) renal impairment received weekly injections of PEG-IFN alfa-2b (1.0 mg kg(-1)) for 4 weeks. Safety assessments were made before each injection and blood samples were taken up to 168 h after the final dose. Results Renal insufficiency increased PEG-IFN alfa-2b exposure. Area under the curve for 0-tau (dosing interval of 168 h), AUC(tau), was increased 30% and 120% in patients with moderate or severe renal insufficiency, respectively. Mean maximum serum concentration was almost doubled in patients with severe insufficiency [1305.8 pg ml(-1); 95% confidence interval (CI) 825, 1786] compared with subjects with normal renal function (731.4 pg ml-1; 95% CI 407, 1056), whereas the apparent volume of distribution was reduced (0.80 I kg(-1) vs. 1.28 l kg(-1), respectively). Elimination half-life was extended in patients with moderate and severe renal insufficiency (65.6 h and 64.9 h, respectively) compared with subjects with normal renal function (51.5 h). Significant differences were observed in the AUC and C-max values of patients with severe renal dysfunction, compared with those who had normal renal function (P < 0.05; Kruskal-Wallis test). PEG-IFN alfa-2b was well tolerated and adverse events were similar in both treatment groups. Conclusions Exposure to PEG-IFN alfa-2b is increased in patients with renal insufficiency, suggesting that doses of the drug should be reduced by 50% in patients with severe renal insufficiency and by 25% in those with moderate insufficiency.