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Physics of Radiation Biology
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
The effective half-life includes both the physical half-life and the biological half-life (time to reduce the radioactivity in the body or in the organ to one half)
Evaluation and Control of Internal Radiation Exposures on the Basis of Committed Dose Equivalent
Published in Kenneth L. Miller, Handbook of Management of Radiation Protection Programs, 2020
The effective half-life of a radionuclide in the body can greatly influence the dose distribution over time. To demonstrate the general concepts regarding the distribution of the internal dose in time and the practicality of the committed and annual dose control systems, consider an exposure of Reference Man under the following extreme situations. It is assumed that Reference Man has a chronic internal exposure over a 50-year period. This chronic exposure results in an intake of 1 stochastic based annual limit on intake (S-ALI) per year of a radionuclide either having (a) an effective half-life very short compared to 1 year or (b) an effective half-life very long compared to 50 years. (See Figures 1 and 2.)
Contrast enhancement agents and radiopharmaceuticals
Published in A Stewart Whitley, Jan Dodgeon, Angela Meadows, Jane Cullingworth, Ken Holmes, Marcus Jackson, Graham Hoadley, Randeep Kumar Kulshrestha, Clark’s Procedures in Diagnostic Imaging: A System-Based Approach, 2020
A Stewart Whitley, Jan Dodgeon, Angela Meadows, Jane Cullingworth, Ken Holmes, Marcus Jackson, Graham Hoadley, Randeep Kumar Kulshrestha
The rate at which a radionuclide is cleared from an organ depends on two factors, the physical half-life of the radionuclide (1/TPl/2) and the rate of biological clearance (1/TBl/2). The radiation dose will be determined by the effective half-life (1/TEl/2) given by the equation:
Current status and prospect for future advancements of long-acting antibody formulations
Published in Expert Opinion on Drug Delivery, 2023
Puneet Tyagi, Garrett Harper, Patrick McGeehan, Shawn P Davis
Significant progress has been made in the development of long-acting presentations of small molecule drugs over the past several decades. More recently, these advances have been extended to peptides and a small number of monoclonal antibodies. In all cases, these approaches have unlocked new value for patients by reducing the frequency of dosing. Patients find less frequent dosing more convenient, less burdensome, and easier to comply with. In addition to the patient value, the companies behind the development of these long-acting presentations benefit from market differentiation from their competitors and the potential of new intellectual property. Physicians are open to long-acting presentations but require confidence in the mechanism behind the extension of the effective half-life and the underlying safety and efficacy of the therapy itself. Regulators maintain high standards for long-acting presentations, just as they do for any new therapy. The onus remains on the developer to gather the necessary data to support the safety and efficacy of their products, but in the new presentations of approved therapies, the existence of data from the original presentation may shorten this development path. The technical solutions to develop long-acting biologics are manifold and include engineering of the protein itself, encapsulation for the sake of controlled release, and formulation and device technologies to allow delivery of large doses. With multiple approaches available, it remains clear that solutions previously applied to small molecule drugs may not be directly applicable and modality-specific solutions are warranted.
New oral protease-activated receptor 4 antagonist BMS-986120: tolerability, pharmacokinetics, pharmacodynamics, and gene variant effects in humans
Published in Platelets, 2022
Samira Merali, Zhaoqing Wang, Charles Frost, Mario Callejo, Michael Hedrick, Lester Hui, Stephanie Meadows Shropshire, Ke Xu, Michel Bouvier, Mary M. DeSouza, Jing Yang
BMS-986120 was readily absorbed after multiple-dose administration of 2.5–100 mg daily; median Tmax was 1.5 hours for each dose on day 1, and at day 14 was 2 hours for all doses except 10 mg (3 hours; Table I). The accumulation index suggests up to a twofold increase in AUC at steady state compared with day 1. Half-life ranged from 57.1 to 80.4 hours; the effective half-life, based upon the accumulation index of BMS-986120 ranged from 18.9 to 24.7 hours. The concentration–time curve after dosing on day 14 shows approximately dose-proportional exposure (Figure 1), consistent with linearity assessments performed for both SAD and MAD data. The pharmacokinetics of midazolam, a sensitive 3A4 substrate, were similar on days –1 and 13, suggesting no notable interaction between BMS-986120 and midazolam (Figure S1).
Novel ligands and modulators of triggering receptor expressed on myeloid cells receptor family: 2015-2020 updates
Published in Expert Opinion on Therapeutic Patents, 2021
Harbinder Singh, Vikrant Rai, Sunil K. Nooti, Devendra K. Agrawal
The classic examples of designed peptides are LR12 and LP17 that were derived from human or mouse TREM-1 complementarity determining regions (CDR) 2 and 3, respectively. CDR-3 corresponds to ‘F’ β strand of extracellular domain of TREM-1, tyrosine residue of which may be responsible to mediate TREM-1 homodimerization and thus disruption in the homeostasis of the physiological processes [4,41]. Peptides LR12 and LP17 block the binding of sTREM-1 to a ligand from mice peritoneal exudate cells [41–45]. Various clinical trials [46,47] have been completed in the recent past to access the safety, tolerability, and pharmacokinetics of LR12 (also known as Nangibotide) in healthy male subjects after its preclinical success [48–51]. Clinical studies revealed that LR12 is safe even at the highest dose tested (10 mg/kg) with mild adverse effects which were considered unrelated to the treatment. Pharmacokinetic studies indicated that its blood concentrations increased in a dose-dependent manner, with the clearance of 6.6 L/kg in healthy subjects of weight 70 kg and thus displayed short effective half-life of about 3 minutes. Even after peptide administration for 28 days, no anti-circulating anti-drug antibodies were found suggesting its safety [46].