To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1a were administered to 3 groups of cynomolgus monkeys (n = 4 each). Plasma concentrations of drug and neopterin, a classic biomarker for IFN-beta PD, were measured at various time-points after dosing. PK/PD profiles were described by noncompartmental methods and pooled data by an integrated mathematical model, where fixed and delayed concentration-time profiles were used as driving functions in an indirect stimulatory response model. PEG-IFN-beta 1a was rapidly absorbed, with peak concentrations observed at about 4-5 h. Compared to previous identical SC doses of IFN-beta la, administration of 1 and 3 MIU/kg of pegylated drug resulted in 27- and 16-fold increases in area under the concentration-time curves. Neopterin concentrations followed a typical dose-dependent biphasic pattern. Pooled PD profiles were well-described by the PK/PD model, and the neopterin elimination rate (0.0190 h(-1)) is consistent with previous estimates. The PEG-modification of IFN-beta la provides enhanced drug exposure and similar pharmacodynamics of neopterin compared to the unmodified formulation.