title: Pharmacokinetics of natural human IFN-alpha in hemodialysis patients.
abstract: A pharmacokinetic study of natural human interferon-alpha (IFN-alpha) was conducted in hemodialysis patients. Natural human IFN-alpha was intramuscularly (i.m.) administered to 8 hemodialysis patients at a single dose of 5 million IU and to 7 patients undergoing hemodialysis at the same dose once daily for 5 successive days. The serum antiviral activity was determined by a cytopathic effect bioassay. In the single dose study, the serum antiviral activity reached a maximum (Cmax) of 56.4 +/- 33.3 IU/ml at 8.3 +/- 2.7 h after dosing, and the area under the serum concentration-time curve (AUC0-24h) was 957.2 +/- 601.8 IU h/ml. The Cmax and AUC0-24h values at day 5 following the repeated dosing were both 2.6-fold higher than those of day 1, and the serum antiviral activity reached a steady state within 3 days after initiation of repeated administration. The serum antiviral activity in hemodialysis patients showed a tendency to increase compared with that in the subjects with normal renal function, but the magnitude of the differences was not great. In one nonhemodialysis patient with poor renal function (creatinine clearance < 30 ml/min), no increases in serum antiviral activity owing to repeated dosing were observed. The main adverse events seen were fever (4 of 13, 30.8%), leukopenia (3 of 13, 23.1%), and fatigue (2 of 13, 15.4%). These results suggest that dosage modifications of natural human IFN-alpha are unnecessary for patients with low renal function, even those undergoing hemodialysis.
authors.affiliation: Department of Urology, Kobe University School of Medicine, Japan.gotoh@med.kobe.-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Gotoh
authors.forename: I
authors.initials: I
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Fujisawa
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Arakawa
authors.forename: S
authors.initials: S
authors.lastname: Kudo
authors.forename: T
authors.initials: T
authors.lastname: Obe
authors.forename: S
authors.initials: S
authors.lastname: Maruyama
authors.forename: R
authors.initials: R
authors.lastname: Sakai
authors.forename: S
authors.initials: S
authors.lastname: Kamidono
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000628:therapy*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000097:blood / Q000493:pharmacokinetics*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha