TY - JOUR
T1 - Single-dose pharmacokinetics and safety of pegylated interferon-α2b in patients with chronic renal dysfunction
AU - Gupta, Samir K.
AU - Pittenger, Amy L.
AU - Swan, Suzanne K.
AU - Marbury, Thomas C.
AU - Tobillo, Emlyn
AU - Batra, Vijay
AU - Sack, Marshall
AU - Glue, Paul
AU - Jacobs, Sheila
AU - Affrime, Melton
PY - 2002/10
Y1 - 2002/10
N2 - This study evaluates the pharmacokinetics and safety of pegylated interferon-α2b (PEG-Intron) following a single- dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel-group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis-dependent group. They received 1 μg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CLCR declined. All subjects reported at least one adverse event, which were typical of those reported after α-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CLCR < 30 ml/min, AUC and Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CLCR, renal clearance accounts for less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.
AB - This study evaluates the pharmacokinetics and safety of pegylated interferon-α2b (PEG-Intron) following a single- dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel-group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis-dependent group. They received 1 μg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CLCR declined. All subjects reported at least one adverse event, which were typical of those reported after α-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CLCR < 30 ml/min, AUC and Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CLCR, renal clearance accounts for less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.
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U2 - 10.1177/009127002401382713
DO - 10.1177/009127002401382713
M3 - Article
C2 - 12362925
AN - SCOPUS:18544362355
SN - 0091-2700
VL - 42
SP - 1109
EP - 1115
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 10
ER -