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• W2023891251 abstract "Thrombopoietin, TPO, a 353 amino acid cytokine, is a primary regulator of platelet production that was cloned recently. A target-mediated (platelet receptors) pharmacokinetic model was developed to characterize the disposition of TPO. Receptor-mediated endocytosis was assigned as the major elimination pathway in the model. A nonspecific binding compartment was also incorporated into the model. TPO concentration vs time profiles from a published phase 1 and 2 clinical trial were used to apply this model. Noncompartmental analysis demonstrated that TPO exhibits nonlinear kinetics. The proposed model captured the concentration-time profiles relatively well. The first-order internalization rate constant was estimated as 0.1 h(-1). The endogenous binding capacity was estimated as 164.0 pM. The second-order binding association constant (k(on)) was 0.055 h(-1).pM(-1) and the first-order dissociation constant (k(off)) was estimated as 2.5 h(-1), rendering the equilibrium dissociation constant K(d) as 45.5 pM. This model may be relevant to other therapeutic agents with receptor-mediated endocytotic disposition." @default.
• W2023891251 created "2016-06-24" @default.
• W2023891251 creator A5017024495 @default.
• W2023891251 creator A5084091087 @default.
• W2023891251 date "2004-03-01" @default.
• W2023891251 modified "2023-09-26" @default.
• W2023891251 title "Pharmacokinetic model of target-mediated disposition of thrombopoietin" @default.
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• W2023891251 doi "https://doi.org/10.1208/ps060109" @default.
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