Pharmacokinetic properties of a 40 kDa branched polyethylene glycol-modified form of consensus interferon-alpha (PEG-CIFN) in rhesus monkeys.
The pharmacokinetic properties of a branched 40 kDa polyethylene glycol (PEG) conjugate formulation of consensus interferon-alpha (CIFN) was evaluated in rhesus monkeys following subcutaneous administration. Four groups of rhesus monkeys (n=6 per group) received 1250, 300 and 150 microg/kg of PEG-CIFN and 150 microg/kg CIFN, respectively. Serum concentrations of the interferons were measured with an antiviral activity assay at various time points after administration. The PK profiles of the pooled data were described by a noncompartmental method. Peak concentration of PEG-CIFN was observed at 27-31 h, followed by a prolonged decay in comparison with the unmodified CIFN, the PEG-CIFN had a 4-5-fold longer terminal half-life. The apparent clearance (dose(sc)/AUC) decreased from 150 mL/h/kg for CIFN to 19.0-45.5 mL/h/kg for PEG-CIFNs. The AUC was lower for PEG-CIFN than that for CIFN at the 150 microg/kg.
Du
Yu
Y
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Tian
Hong
H
Gao
Xiang-Dong
XD
Yao
Wen-Bing
WB
D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D007370:Interferon Type I / Q000493:pharmacokinetics*; D016898:Interferon-alpha; D008253:Macaca mulatta; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins
D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C050739:interferon alfacon-1