Abstract
The pharmacokinetics and clinical response to interferon alpha-2b (IFN) in hemodialysis (HD) patients were studied in order to establish the optimum dosage regimen. The pharmacokinetics of IFN at doses of 3 and 6 million units administered by intravenous infusion over 3 hours was studied during a 6-month course of treatment in HD patients with chronic hepatitis C. Pharmacokinetic parameters for dosing during the HD procedure and between HD procedures were compared with those in hepatitis C patients without renal failure. The maximum serum concentration (Cmax), area under the serum concentration-time curve (AUC) and the half-life (T1/2) of IFN during HD were similar to the values in patients without renal failure. Between HD procedures, however, these parameters were affected by chronic renal failure. At a dose of 3 million units Cmax, AUC and T1/2 between HD procedures were 4.4, 8.7 and 6.9 times greater, respectively, than during HD administration, and at a dose of 6 million units, 5.8, 13.7 and 12.8 times greater, respectively. Clinical outcome was assessed after administration of IFN by intravenous infusion over 3 hours at doses of 3 and 6 million units for 14 consecutive days and then three times weekly for more than three months. After one month of therapy, GPT levels had become in all 4 patients treated at a dose of 3 million units, but all subsequently relapsed and were HCV-RNA-positive one year after the start of therapy. In the 3 patients who received the 6 million unit dose, on the other hand, GPT levels had become normal after one month of therapy, with no relapses or HCV-RNA positivity one year after the start of therapy.
Based on these findings, it is recommended that in HD patients with chronic hepatitis C 3-hour intravenous IFN therapy be started at a dose of 6 million units during the dialysis procedure, and continued for at least 3 months with dose reduction as required.
