Steven W. Martin

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UNLABELLED The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis. INTRODUCTION RANKL is an essential osteoclastic differentiation and activation factor. MATERIALS AND(More)
BACKGROUND Osteoprotegerin (OPG) is a decoy receptor for OPG ligand (OPGL), or receptor activator of NF-kappaB ligand (RANKL). RANKL/RANK interaction is important in terminal differentiation and activation of osteoclasts. In binding to RANKL, OPG blocks differentiation and activation of osteoclasts. AMGN-0007 is a recombinant OPG construct developed as a(More)
The contribution of the lymphatics to the absorption and systemic availability of recombinant human epoetin alfa (rHuEPO) following s.c. injection was examined using a cannulated sheep model. Parallel studies were conducted in sheep where a single bolus dose was administered either by i.v. (10, 100, or 1000 IU/kg) or s.c. (400 IU/kg) injection. The first(More)
The node of Ranvier is a complex macromolecular assembly of ion channels and other proteins that is specialized for the rapid propagation of the action potential. A full understanding of the processes responsible for the assembly and maintenance of the node requires first the identification and characterization of the proteins found there. Here we show that(More)
To determine the contribution of the lymphatics to the systemic availability of darbepoetin alfa (DA) using an established sheep model. DA was administered either by intravenous (IV) injection (0.2, 0.5 or 2 μg/kg) or by subcutaneous (SC) administration (2 μg/kg) into the interdigital space of the hind leg. A SC control group was used to determine the(More)
BACKGROUND AND AIMS Leucocyte migration to gut mucosa, mediated by integrin binding to mucosal addressin cell adhesion molecule (MAdCAM), is a promising target for therapeutic intervention in inflammatory bowel disease. This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this(More)
Purpose. The purpose of this work was to develop a pharmacokinetic model to describe the contribution of the lymphatics to the absorption and bioavailability of r-metHu-Leptin administered by subcutaneous (SC) injection to sheep. Methods. r-metHu-Leptin was administered either by bolus intravenous injection (0.1 mg/kg) into the jugular vein or by SC(More)
Osteoprotegerin (OPG) is a naturally occurring negative regulator of osteoclast differentiation, activation, and survival. We created a recombinant form of human OPG (rhOPG), with a sustained serum half-life, to achieve prolonged antiresorptive activity. This study describes the rapid and sustained antiresorptive effects that are achieved with a single(More)
Prediction of human pharmacokinetics (PK) can be challenging for monoclonal antibodies (mAbs) exhibiting target-mediated drug disposition (TMDD). In this study, we performed a quantitative analysis of a diverse set of six mAbs exhibiting TMDD to explore translational rules that can be utilized to predict human PK. A TMDD model with rapid-binding(More)
The combretastatins are derived from an African medicinal plant Combretum caffrum (Combretaceae). They have previously been shown to be potent inhibitors of microtubule assembly that cause marked haemorrhagic necrosis in murine subcutaneous tumors. Promising clinical trial results with combretastatin A-4 phosphate led to this investigation of the anti-tumor(More)