Multiple-dose pharmacokinetics of peginterferon alfa-2b in patients with renal insufficiency.
OBJECTIVE
To evaluate the safety, tolerability and multiple-dose pharmacokinetics of pegylated interferon (PEG-IFN) alfa-2b in patients with moderate or severe renal insufficiency and in those with normal renal function.


METHODS
In an open-label study, subjects with normal renal function (creatinine clearance >80 ml min(-1) per 1.73 m2) and patients with moderate (30-50 ml min(-1) per 1.73 m2) or severe (10-29 ml(-1) min(-1) per 1.73 m2) renal impairment received weekly injections of PEG-IFN alfa-2b (1.0 microg kg(-1)) for 4 weeks. Safety assessments were made before each injection and blood samples were taken up to 168 h after the final dose.


RESULTS
Renal insufficiency increased PEG-IFN alfa-2b exposure. Area under the curve for 0-tau (dosing interval of 168 h), AUC(tau), was increased 30% and 120% in patients with moderate or severe renal insufficiency, respectively. Mean maximum serum concentration was almost doubled in patients with severe insufficiency [1305.8 pg ml(-1); 95% confidence interval (CI) 825, 1786] compared with subjects with normal renal function (731.4 pg ml(-1); 95% CI 407, 1056), whereas the apparent volume of distribution was reduced (0.80 l kg(-1)vs. 1.28 l kg(-1), respectively). Elimination half-life was extended in patients with moderate and severe renal insufficiency (65.6 h and 64.9 h, respectively) compared with subjects with normal renal function (51.5 h). Significant differences were observed in the AUC and C(max) values of patients with severe renal dysfunction, compared with those who had normal renal function (P < 0.05; Kruskal-Wallis test). PEG-IFN alfa-2b was well tolerated and adverse events were similar in both treatment groups.


CONCLUSIONS
Exposure to PEG-IFN alfa-2b is increased in patients with renal insufficiency, suggesting that doses of the drug should be reduced by 50% in patients with severe renal insufficiency and by 25% in those with moderate insufficiency.
Gupta
Samir K
SK
Schering-Plough Research Institute, Kenilworkth, NJ 07033, USA. samir.gupta@spcorp.com
Swan
Suzanne K
SK
Marbury
Thomas
T
Smith
William
W
Schwartz
Sherwyn
S
Kolz
Karen
K
Cutler
David L
DL
D000293:Adolescent; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D051437:Renal Insufficiency / Q000097:blood* / Q000188:drug therapy*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b