title: Recombinant leukocyte a interferon treatment in patients with chronic hepatitis B virus infection. Pharmacokinetics, tolerance, and biologic effects.
abstract: Large doses of recombinant leukocyte A interferon were administered to 20 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis B to study the maximum tolerated dose, its pharmacokinetics, and its antiviral activity. The first group of 5 patients received a constant dose of 36 X 10(6) U/day for 28 consecutive days. When it was well tolerated, the second, third, and fourth groups (5 patients each) received 50, 72, and 100 X 10(6) U/day, respectively. All 20 patients completed the 28-day treatment. Hourly and daily profile of serum interferon level showed a dose-dependent effect with an increasing dosage, and cumulative effects during the treatment. The mean peak serum interferon concentration ranged from 93 U/ml on day 1 in the first group to 1271 U/ml on day 28 in the fourth group. Inhibition of serum deoxyribonucleic acid polymerase activity and hepatitis B virus-deoxyribonucleic acid during the treatment was compared between the groups with low doses (36 and 50 X 10(6) U) and high doses (72 and 100 X 10(6) U). Low doses of interferon suppressed deoxyribonucleic acid polymerase activity to the same extent as did the high doses. Prednisolone withdrawal was combined with interferon in 5 patients. Three patients treated with such combination became seronegative for hepatitis B e antigen during the treatment, whereas all 15 with interferon alone remained seropositive. These results suggest that a maximum antiviral effect of recombinant leukocyte A interferon is below the maximum tolerated doses.
mesh_terms: D000328:Adult; D001831:Body Temperature; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis; D004259:DNA-Directed DNA Polymerase / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000201:enzymology / Q000628:therapy*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D007370:Interferon Type I; D011239:Prednisolone; D004259:DNA-Directed DNA Polymerase