Single dose pharmacokinetics (PK) of peg-interferon alfa-2B (P) in subjects with various degrees of chronic renal insufficiency

P is under development for the treatment of chronic hepatitis C. This open-labeled study evaluated the PK of P in 26 subjects (20 renally impaired, 6 healthy). Age ranged from 32 to 67 years. Subjects received a single 1.0 μg/kg subcutaneous injection and had blood samples collected for up to 168 hours after dosing. Hemodialysis (HD) subjects received two doses separated by 3 weeks to assess inter- and intra-dialytic clearances. Mean (%CV) PK Parameters for P: CLcr AUCtf t1/2 CL/FV d/F (ml/min) (pg·hr/ml) (hr) (ml/min) (L) >80 51251(31) 40.1(18) 26.4(35) 87.9(27) 50-79 64379 (na) 45.1 (na) 25.9 (na) 65.8 (na) 30-49 86713(39) 48.1(32) 16.8(28) 66.6(27) 10-29 97195(32) 55.6(24) 14.3(32) 66.6(26) Inter HD 102802(21) 51.9(35) 12.9(24) 60.8(53) Intra HD 96281(19) 63.7(35) 12.7(32) 72(51) P AUC and t1/2 were increased in patients with CRI compared with controls. HD had a minimal effect on P clearance. Regression analysis for CL/F and CLcr suggests a portion of P clearance is renally mediated.