Subject(s)
Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Pyrrolidinones/administration & dosage , Pyrrolidinones/pharmacokinetics , Adult , Anticonvulsants/adverse effects , Anticonvulsants/blood , Biological Availability , Cross-Over Studies , Female , Humans , Male , Middle Aged , Pyrrolidinones/adverse effects , Pyrrolidinones/blood , Solutions , Tablets , Therapeutic Equivalency , Young AdultABSTRACT
Interleukin-6 (IL-6) is implicated in the pathophysiology of several inflammatory conditions. Olokizumab, a humanized anti-IL-6 monoclonal antibody, selectively blocks the final assembly of the IL-6 signaling complex. A randomized, double-blind, placebo-controlled, phase I dose-escalation study assessed the safety and tolerability of escalating single doses of olokizumab administered intravenously (iv) or subcutaneously (sc) to 67 healthy male volunteers. The pharmacokinetics, pharmacodynamics and immunogenicity of olokizumab were also assessed. Olokizumab was tolerated at doses up to 3.0 mg/kg sc and 10.0 mg/kg iv; the maximum tolerated dose was not reached. No serious adverse events or withdrawals as a result of treatment-emergent adverse events were reported. Pharmacokinetic analysis showed that both maximum serum concentration and area under the concentration-time curve increased linearly with increasing dose. Mean terminal half-life was 31.5 days (standard deviation 12.4 days). The bioavailability of the sc doses ranged from 84.2% to 92.5%. Rapid decreases in C-reactive protein concentrations were observed, with no dose dependency.
Subject(s)
Anti-Inflammatory Agents/pharmacokinetics , Antibodies, Monoclonal, Humanized/pharmacokinetics , Adolescent , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/blood , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/blood , Area Under Curve , Biological Availability , Double-Blind Method , Drug Monitoring/methods , Germany , Half-Life , Healthy Volunteers , Humans , Infusions, Intravenous , Infusions, Subcutaneous , Linear Models , Male , Metabolic Clearance Rate , Middle Aged , Models, Biological , Young AdultABSTRACT
Chronic illness combined with functional impairment often results in an increased need for medical care and supportive long-term care (LTC) services. Navigating the health care system is challenging and complex, and even more so for patients with complex needs. Traditional fee-for-service care does not support and facilitate coordination and collaboration between providers and service settings. In New York State, managed LTC, a model of coordinated care for the chronically ill, endeavors to provide a bridge between primary, acute, home and community-based, and institutional LTC services for a medically complex and functionally frail nursing home eligible population.
