2', 5'-OAS induction, as a consequence of the enhanced PK exposure of PEG-IFN. The current PK/PD model well describes the enhanced PD effect, i.e. 10 ng/mL) which may indicate that 180 μg is the clinically optimal dose because the serum level of PEG-IFN at a dose of 180 μg sustained above EC 50 for long time in comparison with the case at a dose of 90 μg and 2', 5'-OAS activity reached a plateau level at a dose of 180 μg, although 2', 5'-OAS activity has not been validated as a surrogate marker of clinical activity. The mean EC 50 at a dose of 180 μg was one-third of its C max (ca. The PK of PEG-IFN can be described by a linear process.
2', 5'-OAS activity.Ī first-order absorption model was concluded to be the best absorption model to describe PK/PD of PEG-IFN and 2', 5'-OAS activity. An indirect response model (stimulation-k in 0) was used to describe PD of PEG-IFN, i.e. Four different absorption models were compared in the present study to establish a PK/PD model for PEG-IFN and provide an optimal dosage guideline, where 2', 5'-oligoadenylate synthetase (2', 5'-OAS) is used as the PD marker. The half-life of interferon increases upon pegylation and the absorption is sustained, thereby providing greater exposure and the expectation of greater efficacy with just weekly administrations. Pegylated interferon α-2a (PEG-IFN) is interferon α-2a in which one branched polyethylene glycol molecule is conjugated.
Thus, the most suitable PK/PD model must be used appropriately to avoid reaching a local minimum of fitting results.
Data analysis of biological proteins presents a challenge because errant points may indeed reflect the true pharmacokinetic profile of the agent under study.
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