PHARMACOKINETICS OF ALPHA-IFN-2B IN CHRONIC HEPATITIS-C VIRUS PATIENTS UNDERGOING CHRONIC-HEMODIALYSIS OR WITH NORMAL RENAL-FUNCTION - CLINICAL IMPLICATIONS

In this prospective controlled study, the pharmacokinetic profiles of alpha-interferon 26 (alpha IFN-2b) were determined by the enzyme-linke d immunosorbent assay method in hepatitis C virus-positive (HCV+) dial ysis and nonuremic patients, after a single subcutaneous injection of 3 million units. Ten HCV+/RNA+ patients (group A) with a normal renal function (mean serum creatinine: 1.03 +/- 0.26 [SD] mg/dl) and 10 HCV/RNA+ patients undergoing chronic hemodialysis (group B) were included . The pharmacokinetic profiles of alpha IFN were determined after the very first subcutaneous injection of the drug. Plasma alpha IFN concen trations were determined before the injection and then 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, and 36 h after the injection. They were ass essed by means of an enzyme-linked immunosorbent assay test. Patients from both groups had a similar body surface area. It was found that in group B: (I) the mean maximum (SD) serum alpha IFN concentration (C-m ax) was significantly higher (52 +/- 12 pg/ml) than in group A (39 +/- 12 pg/ml; P = 0.03); (2) the time at which C-max occurred (T-max) was significantly higher (10 +/- 3 h) than in group A (7.5 +/- 2 h; P = 0 .05); (3) the observed area under the plasma alpha IFN concentration-t ime curve was about twice as much, i.e., 936 +/- 212 pg x h/ml, as tha t for group A (485 +/- 184 pg x h/ml; P < 0.0001); and (4) the alpha I FN half-life was significantly longer (9.6 +/- 2.9 h) than in group A (5.3 +/- 1.3 h). As early as 24 h after the alpha IFN injection was gi ven, the drug was no longer detectable in nonuremic patients' sera, wh ereas It could be detected up to the next injection in all of the dial ysis patients' sera. When trough levels of alpha IFN were measured jus t before the 10th injection, they were always below the threshold leve l in the 10 patients from group A, ie., 4.1 pg/ml, whereas in group B they were measurable for four of nine patients (P = 0.05) and ranged b etween 5.8 and 36.1 pg/ml. Severe neurologic side effects were observe d only in group B, ie., in three patients. Hemoglobin levels did signi ficantly decrease but only in group B patients, and this was significa ntly correlated with the C-max (r = 0.67; P = 0.03). This is the first controlled study to demonstrate that the clearance of aIFN is about t wice as low in dialysis patients as in nonuremic patients. These resul ts might be of relevance when deciding the optimal alpha IFN therapy s cheme for HCV+ patients, either with normal renal function or undergoi ng chronic hemodialysis.